Method of treating an overactive bladder condition

ABSTRACT

A method of treating an overactive bladder condition includes providing a stimulation device having a generator enclosing a primary cell that is coupled to circuitry, and a lead coupling an electrode assembly to the generator, where the circuitry is operable to generate a stimulation signal with a duty cycle of between 0.1% and 2.5% and a total average current drain from the primary cell of between 0.1 μA and 5 μA, with the total average current drain including a background current plus a stimulation current weighted by the duty cycle; forming an incision in skin of a patient diagnosed with the overactive bladder condition; implanting the stimulation device in the patient by inserting the stimulation device into the incision in the skin of the patient; and closing the incision.

CROSS-REFERENCE

This application is a continuation of U.S. patent application Ser. No.16/654,717, filed Oct. 16, 2019; which is a continuation of U.S. patentapplication Ser. No. 16/222,246, filed Dec. 17, 2018, now U.S. Pat. No.10,532,208 issued on Jan. 14, 2020; which is a continuation of U.S.patent application Ser. No. 15/880,373, filed Jan. 25, 2018, now U.S.Pat. No. 10,195,425 issued on Feb. 5, 2019; which is a continuation ofU.S. patent application Ser. No. 15/424,683, filed Feb. 3, 2017, nowU.S. Pat. No. 9,913,980 issued on Mar. 13, 2018; which is a continuationof PCT Application No. PCT/US15/45138, filed Aug. 13, 2015; which claimsthe benefit of U.S. Provisional Applications No. 62/038,308, filed Aug.17, 2014, 62/038,316, filed Aug. 17, 2014, and 62/102,543, filed Jan.12, 2015; which applications are incorporated herein by reference.

BACKGROUND

The present disclosure relates to medical devices, systems, and methods.In particular, the present disclosure relates to medical devices,systems, and methods for stimulating tissue such as nerves to treatvarious indications. Indications of interest may include urinary andbowel incontinence, for example. Stimulation devices and therapies forurinary and bowel incontinence are currently available in themarketplace but may be limited in at least some cases.

A sacral nerve stimulator, InterStim II, marketed by Medtronic Inc., ofFridley, Minn., provides therapy for urinary or bowel incontinencethrough the use of electrical stimulation of the sacral nerve by along-term active implantable device. The InterStim II implantablegenerator is large, at 14 cc, and must be implanted in the upperbuttock. A long lead wire, 33 cm, must then be tunneled to thestimulation site. The generator typically lasts approximately 4.4 yearsdue to the relatively high duty-cycle stimulation requirement of 16seconds ON, 8 seconds OFF at an amplitude of 3 V, rate of 14 Hz andpulse width of 210 μs.

InterStim patients undergo an invasive qualification step before thegenerator is implanted, to verify that the therapy has a high likelihoodof success. The qualification step requires the implantation of atemporary electrode connected to a transcutaneous wire that plugs intoan external neurostimulator carried by the patient, typically for 3 to 5days.

PTNS (Percutaneous Tibial Nerve Stimulation), marketed by Uroplasty,Inc, of Minnetonka, Minn., also provides therapy for urinaryincontinence through electrical stimulation of the tibial nerve via apercutaneous needle electrode. Electrical stimulation is provided by anexternal stimulator programmed to delivery therapy for approximately 30minutes. Initially patient sessions are typically scheduled once perweek. Sessions can be scheduled less frequently once effective reliefoccurs.

Accordingly, there are needs for devices, systems, and methods forstimulation that address one or more of the above drawbacks such aslarge and uncomfortable implant size, low implant lifespan, invasivequalification steps, and too frequent patient sessions, to name a few.

SUMMARY

The present disclosure provides devices, systems, and methods forstimulating tissue. Disclosed is a miniature implantable neurostimulatorfor sciatic nerves and their branches providing therapy for urinary andbowel incontinence. The implanted neurostimulator is significantlysmaller in volume than existing sacral neurostimulators whilemaintaining a medically-acceptable device longevity. By stimulatingbranches of the sciatic nerve and locating the miniature neurostimulatorin the leg, the present disclosure provides an implantable alternativeto sacral nerve stimulation, with a device that is potentially simplerto implant, safer, and more comfortable for patients.

Aspects of the present disclosure may provide methods for improving aurinary or bowel function in a subject. An incision may be created in aleg of a patient to access a stimulation site. An implant at or near thestimulation site may be placed through the incision. At least a portionof an electrode assembly of the implant may be positioned at or adjacenta sciatic nerve or a branch thereof in the stimulation site. Theelectrode assembly of the implant may direct a stimulation signal to thetissue of the subject. The stimulation signal may improve a urinary orbowel function in the subject, such as to treat urinary incontinence(e.g., overactive bladder (OAB) or bowel incontinence (BI). Thestimulation signal may be directed with a low duty cycle of between 0.1%and 2.5%. The stimulation signal may be directed with a low currentdrain of a battery of the implant of between 0.1 μA and 5 μA. The lowduty cycle and low current drain of the stimulation pulse may combine toprovide a useful life of the implant in the body of at least 5 yearswithout removal from the body.

The step of creating the incision in the leg may comprise a step ofcreating a tunnel in the leg for the implant. A first tunnel may becreated from the incision into the tissue, and a second tunnel may becreated from the incision into the tissue as well. To place the implantat or near the stimulation site, an enclosure of the implant may beplaced into the first tunnel. To position the electrode assembly of theimplant at or adjacent a sciatic nerve or a branch thereof, at least aportion of the electrode assembly may be positioned in the secondtunnel. The first tunnel may be created in a first direction and thesecond tunnel may be created in a second direction opposite the firstdirection. The tunnel(s) in the leg is created with a blunt dissectiontool. The blunt dissection tool may comprise an elongate rod with a ballnose at a first end and a handle on a second end opposite the first end.The elongate rod may be made of stainless steel and the handle may bemade of a plastic or polymer. At least a portion of the blunt dissectiontool may be radiopaque.

The step of creating the incision in the leg may comprise a step ofcreating a primary incision in the leg to access the stimulation site,creating a secondary incision in the leg, and creating a tunnel in theleg between the primary and secondary incisions. To place the implant inthe stimulation site, the implant may be placed in the tunnel and theimplant may be fixated in place through one or more of the primary orsecondary incisions, such as by suturing. After the incision in the legis made and the implant placed at or near the stimulation site, theincision may be closed.

Prior to placing the implant at or near the stimulation site ordirecting the stimulation signal to the tissue of the subject, thesubject may be qualified for use of the implant. The subject may bequalified by applying a therapy from an external device to the subjectto test the therapy with the subject. The qualifying therapy may beapplied by percutaneously or transcutaneously stimulating the tissuewith a signal generated from the external device, such as with itselectrode array.

Not all OAB patients respond to neuromodulation. Consequently, users canchoose to qualify patients before implanting a permanent pulse generatorand lead. Percutaneous tibial nerve stimulation (PTNS), which may use aneedle electrode and an external pulse generator, for example, during 12weekly clinic visits, may be used to qualify patients. Alternatively orin combination, a percutaneous implantation of a temporaryelectrode-lead with no fixation feature may be performed and a wearableexternal pulse generator may be used for a trial period, for example,stimulating for 30 minutes each day for one or two weeks. The temporaryelectrode-lead can be removed without a surgical procedure.Alternatively or in combination, a permanent electrode-lead with afixation feature may be implanted and a wearable external pulsegenerator may be used for a similar trial period. The use of thepermanent lead can have a potential advantage of preventingfalse-negative qualifications due to electrode dislodgment or migration,but it may have a potential disadvantage of requiring responders andnon-responders to undergo two surgical procedures. Alternatively, thepermanent electrode-lead and pulse generator may be implanted without aprevious qualification period (“straight to implant”).

The useful life of the implant implanted in the body may be in a rangebetween 5 and 35 years, 6 and 34 years, 7 and 33 years, 8 and 32 years,9 and 31 years, 10 and 30 years, 11 and 29 years, 12 and 28 years, 13and 27 years, 14 and 26 years, 15 and 25 years, 16 and 24 years, 17 and23 years, 18 and 22 years, or 19 and 21 years. The background currentdrain may be in a range between 4.5 μA and 0.10 μA, 4.0 μA and 0.10 μA,3.5 μA and 0.10 μA, 3.0 μA and 0.10 μA, 2.5 μA and 0.10 μA, 2.0 μA and0.10 μA, 1.5 μA and 0.10 μA, 1.0 μA and 0.10 μA, 0.9 μA and 0.10 μA, 0.8μA and 0.10 μA, 0.7 μA and 0.10 μA, 0.6 μA and 0.10 μA, 0.5 μA and 0.10μA, 0.4 μA and 0.10 μA, 0.3 μA and 0.10 μA, or 0.2 μA and 0.1 μA.

The duty cycle of the stimulation signal may be in a range between 2.4%and 0.1%, 2.3% and 0.1%, 2.2% and 0.1%, 2.1% and 0.1%, 2.0% and 0.1%,1.9% and 0.1%, 1.8% and 0.1%, 1.7% and 0.1%, 1.6% and 0.1%, 1.5% and0.1%, 1.4% and 0.1%, 1.3% and 0.1%, 1.2% and 0.1%, 1.1% and 0.1%, 1.0%and 0.1%, 0.9% and 0.1%, 0.8% and 0.1%, 0.7% and 0.1%, 0.6% and 0.1%,0.5% and 0.1%, 0.4% and 0.1%, 0.3% and 0.1%, or 0.2% and 0.1%. Forexample, the electrode assembly of the implant may direct thestimulation signal to the tissue of the subject for about 30 minutesonce a week. In some cases, the electrode assembly of the implant maydirect the stimulation signal to the tissue of the subject while thesubject is asleep. Alternatively or in combination, the stimulation maybe applied as the user, patient, or medical professional desires. PTNSapplied once per week can take six weeks or more to show an effect.Patients who are desperate for an immediate cure could prefer morefrequent stimulation at the start of therapy. Consequently, theimplantable pulse generator of the implant can be configured tostimulate frequently just after implant to provide a faster response,and can then taper to less frequent stimulation afterwards to meetlongevity objectives. This schedule can be preprogrammed or modified asnecessary in real time, by the user, patient, or medical professional.

The stimulation signal may have a stimulation current in a range between19 mA and 1 mA, 18 mA and 2 mA, 17 mA and 3 mA, 16 mA and 4 mA, 15 mAand 5 mA, 14 mA and 6 mA, 13 mA and 7 mA, 12 mA and 8 mA, or 11 mA and 9mA. The generated stimulation signal may be charged balanced. Thegenerated stimulation signal has a stimulation frequency or stimulationpulse rate in a range between 30 Hz and 10 Hz, 29 Hz and 11 Hz, 28 Hzand 12 Hz, 27 Hz and 13 Hz, 26 Hz and 14 Hz, 25 Hz and 15 Hz, 24 Hz and16 Hz, 23 Hz and 17 Hz, 22 Hz and 18 Hz, or 21 Hz and 19 Hz. Forexample, the stimulation frequency may be from 20 Hz to 25 Hz, which arange shown to be effective to treat urinary and/or bowel incontinencewith tibial nerve stimulation. The generated stimulation signal may havea stimulation pulse width in a range between 300 μs and 100 μs, 290 μsand 110 μs, 280 μs and 120 μs, 270 μs and 130 μs, 260 μs and 140 μs, 250μs and 150 μs, 240 μs and 160 μs, 230 μs and 170 μs, 220 μs and 180 μs,or 210 μs and 190 μs. For example, a pulse pattern with 200 μs pulses at20 Hz may be used because this pattern has been shown effective for totreat urinary and/or bowel incontinence with tibial nerve stimulation.

In other embodiments, different pulse patterns may be applied. Forexample, aspects of the present disclosure may encompass the treatmentof other indications aside from urinary and/or bowel incontinence may betreated with different pulse patterns. Stimulation pulse patterns from90 to 500 μs at 20 to 100 Hz may be applied and these patterns have beenshown effective for relief from peripheral nerve pain. For peripheralnerve field stimulation, most patients prefer the frequency to bebetween 20 and 50 Hz. Anything higher than this range may be felt as avery strong sensation, or cause burning or pinching. Pulse width in therange of 90 to 250 μs may be best tolerated. Stimulation at higherfrequencies, e.g. 1,200 Hz, have also been shown effective for relieffrom peripheral nerve pain and may have an additional advantage of notprovoking a sensory response in the patient. The stimulation signal maybe generated with such high frequencies.

The implant may have a size and/or shape such that it is implanted inthe body of the subject with minimal long-term discomfort. For example,the total volume of the implant is in a range between 1.9 cc and 0.1 cc,1.8 cc and 0.2 cc, 1.7 cc and 0.3 cc, 1.6 cc and 0.4 cc, 1.5 cc and 0.5cc, 1.4 cc and 0.6 cc, 1.3 cc and 0.7 cc, 1.2 cc and 0.8 cc, or 1.1 ccand 0.9 cc. The implant may be cylindrical, tubular, or rectangular inshape, for example.

In exemplary embodiments, the implant has a longevity exceeding 5 yearsin a 1.0 cc volume and is suitable for implantation near the posteriortibial nerve. For example, the enclosure or housing of the implant maybe 7 mm in diameter and 25 mm long. In addition to being suitable totreat urinary and/or bowel incontinence, the device design and formfactor may be appropriate for other therapies for which intermittentstimulation has been demonstrated effective: Such therapies include, butare not limited to: (a) intermittent sphenopalatine ganglion stimulation(SPGS) for headaches; (b) bilateral supraorbital nerve stimulation(SNSt) for headaches at 20 minutes per day; (c) vagus nerve stimulationfor epilepsy and depression at 30 seconds every 5 minutes; (d) PTNS forpelvic pain; and, (e) stimulation in the infraorbital foramina forneuropathic pain.

The implant may be powered in many ways. The battery of the implant maybe a primary battery. The circuitry of the implant may have a lowcurrent drain such that the primary battery may be effective for manyyears. The battery of the implant may be rechargeable and may berecharged wirelessly. The recharging power may be furnished from anexternal (non-implanted) device during a charging period. The implantmay have no battery, with power furnished from an external(non-implanted) device when stimulation is required.

One or more of a housing or enclosure of the implant or the electrodearray may be anchored into the tissue with a fixation element of thehousing or electrode array. The fixation element may comprise a hook, apin, a screw, a pigtail screw, a ring, a grasper, or a suture, to name afew examples. To position the electrode assembly at or adjacent thesciatic nerve or the branch thereof, the nerve or branch may beencircled with a cuff of the electrode assembly.

In some embodiments, the lead may have rod electrodes as opposed to cuffelectrodes. The lead can be implanted with a dilator and introducer. Theuser can employ an introducer and dilator to tunnel from the incision toa site near the nerve. Then, the user can advance the lead through theintroducer and remove the introducer. Following that, the user canemploy the blunt dissection tool to tunnel in the other (cranial)direction from the incision and can place the pulse generator there.Consequently, the procedure generally does not expose the stimulationsite nor the pulse generator site.

The electrode assembly may at least partially be separated from thehousing or enclosure by a lead. The stimulation signal may be unipolar,bipolar, or tripolar. The electrode assembly may comprise a returnassembly placed on the exterior of the housing or enclosure of theimplant. Alternatively or in combination, at least two electrodes may beon a lead and separated from the housing or enclosure to avoidstimulating muscle at the housing or enclosure.

The pulse generator at the housing or enclosure of the implant may beconnected to the lead in many ways. In some embodiments, the lead doesnot have a connector detachable from the pulse generator, but insteadconnects permanently to the pulse generator, simplifying constructionand improving reliability. In some embodiments, the lead has a connectordetachable from the pulse generator. This detachability can allow theuser to implant the lead for a qualification period, and then, ifqualification is successful, to implant a pulse generator and connect itto the previously-implanted lead. The detachability also can facilitateimplantation with a single incision, where the pulse generator isimplanted cranial to the incision, and the lead is implanted caudal tothe incision.

A wireless communication transceiver of the implant may communicate withan external programmer. In communicating with the wireless communicationtransceiver, the external programmer may receive one or more of acurrent of the battery, a voltage of the battery, time, a therapystatus, a waveform of the generated stimulation signal, a deviceorientation, a device alignment, or other implant information orcommand. The external programmer may display the various statuses of theimplant. In some embodiments, the external programmer is incommunication with a printing device to record a therapeutic protocoldelivered by the implant.

The wireless communication transceiver may communicate with the externalprogrammer through one or more of a Bluetooth connection, a Bluetooth LEconnection, a Zigbee connection, a Wi-Fi connection, an IR connection,an RF connection, an ultrasound-based connection, a WiMax connection, anISM connection, an AM connection, an FM connection, a conductiveconnection, or a magnetic connection. In many embodiments, the externalprogrammer may send signals to the implant by interfacing with theimplant using a magnetic field and the programmer may receivecommunication signals back electrically conducted from the implant.These conductive communications signals may be generated by the pulsegenerator so as not to stimulate any nerve, muscle, or other tissue. Forexample, the communication signal may be one or more of below athreshold stimulation pulse amplitude, below a threshold stimulationpulse duration, or during a refractory period of a nerve, muscle, orother tissue. The generated conductive communication signals may be lowpower and generated with low current drain, further contributing to thelong useful life of the implant.

The external programmer may come in many forms. The external programmermay comprise one or more of a key fob, a smartphone, a smartwatch, atablet computer, a laptop computer, a wearable computing device, a strapconfigured to at least partially encircle a limb of the subject, orother portable computing device. For example, the external programmermay comprise a wearable magnetic field generator and the wearablemagnetic field generator may be aligned to optimize magneticcommunication with the wireless communication transceiver of the implantwhen worn.

In some embodiments, the external programmer may be used to stimulatetissue and the external programmer may itself comprise a tissuestimulator. For example, the tissue stimulator may comprise one or moreof a percutaneous tibial nerve stimulator or a transcatheter electricalnerve stimulator.

The implant may be configured to detect a magnetic field. The generationof the stimulation signal may be postponed, disabled, or otherwisemodified in response to the detected magnetic field. The magnetic fieldmay be generated from an external programmer to communicate with thecircuitry of the implant. The magnetic field may be detected with amagnetic field sensor such as a giant magnetoresistance (GMR) switch,which is small, light, and reliable. The magnetic field comprises an MRIfield. For example, when an MRI field is detected, the implant or atleast the stimulation signals generated may be switched off. Moretypically, the magnetic field sensor may detect signals from theexternal programmer such as to receive instructions. In addition, thepatient or medical professional can apply a permanent magnet in vicinityof the implanted pulse generator, for postponing, modifying, or stoppingtherapy; for example if therapy becomes unpleasant or ineffective.

An orientation or alignment of the implant may be detected, such as withan accelerometer of the implant. The generation of the stimulationsignal may be disabled, postponed, or otherwise modified in response tothe detected orientation or movement.

Aspects of the present disclosure may also provide implantable devicesfor permanent implantation in a body of a subject for long-term use tostimulate tissue. An exemplary device may comprise an enclosure anenclosure configured to be implanted in a body of a subject, circuitrydisposed within the enclosure, a battery disposed within the enclosureand coupled to the circuitry, an electrode assembly coupled to theenclosure and the circuitry, and a lead coupling the electrode assemblyto the enclosure and separating at least a portion of the electrodeassembly from the enclosure. The circuitry may be configured to generatea stimulation signal with a low duty cycle of between 0.1% and 2.5% anda low background current drain of between 0.1 μA and 5 μA. The batterymay provide power to the circuitry to generate the stimulation signal.The electrode assembly may be configured to direct the generatedstimulation signal to the tissue of the subject. The low duty cycle andlow current drain of the generated stimulation signal may combine toprovide a useful life of the implantable device implanted in the body ofat least 5 years without removal from the body.

The useful life of the implantable device may be in a range of between 5and 35 years, 6 and 34 years, 7 and 33 years, 8 and 32 years, 9 and 31years, 10 and 30 years, 11 and 29 years, 12 and 28 years, 13 and 27years, 14 and 26 years, 15 and 25 years, 16 and 24 years, 17 and 23years, 18 and 22 years, or 19 and 21 years. The background current drainmay be in a range of between 4.5 μA and 0.10 μA, 4.0 μA and 0.10 μA, 3.5μA and 0.10 μA, 3.0 μA and 0.10 μA, 2.5 μA and 0.10 μA, 2.0 μA and 0.10μA, 1.5 μA and 0.10 μA, 1.0 μA and 0.10 μA, 0.9 μA and 0.10 μA, 0.8 μAand 0.10 μA, 0.7 μA and 0.10 μA, 0.6 μA and 0.10 μA, 0.5 μA and 0.10 μA,0.4 μA and 0.10 μA, 0.3 μA and 0.10 μA, or 0.2 μA and 0.1 μA.

The duty cycle of the stimulation signal may in a range of between 2.4%and 0.1%, 2.3% and 0.1%, 2.2% and 0.1%, 2.1% and 0.1%, 2.0% and 0.1%,1.9% and 0.1%, 1.8% and 0.1%, 1.7% and 0.1%, 1.6% and 0.1%, 1.5% and0.1%, 1.4% and 0.1%, 1.3% and 0.1%, 1.2% and 0.1%, 1.1% and 0.1%, 1.0%and 0.1%, 0.9% and 0.1%, 0.8% and 0.1%, 0.7% and 0.1%, 0.6% and 0.1%,0.5% and 0.1%, 0.4% and 0.1%, 0.3% and 0.1%, or 0.2% and 0.1%. Forexample, the electrode assembly of the implantable device may direct thestimulation signal to the tissue of the subject for about 30 minutesonce a week. In some cases, the electrode assembly of the implant maydirect the stimulation signal to the tissue of the subject while thesubject is asleep. Alternatively or in combination, the stimulation maybe applied as the user, patient, or medical professional desires asdescribed above and herein. Any scheduled stimulation can bepreprogrammed or modified as necessary in real time, by the user,patient, or medical professional.

The circuitry may be configured to generate the stimulation signal tohave a current in a range of between 19 mA and 1 mA, 18 mA and 2 mA, 17mA and 3 mA, 16 mA and 4 mA, 15 mA and 5 mA, 14 mA and 6 mA, 13 mA and 7mA, 12 mA and 8 mA, or 11 mA and 9 mA. The generated stimulation signalmay be charged balanced. The generated stimulation signal has astimulation frequency or stimulation pulse rate in a range between 30 Hzand 10 Hz, 29 Hz and 11 Hz, 28 Hz and 12 Hz, 27 Hz and 13 Hz, 26 Hz and14 Hz, 25 Hz and 15 Hz, 24 Hz and 16 Hz, 23 Hz and 17 Hz, 22 Hz and 18Hz, or 21 Hz and 19 Hz. For example, the stimulation frequency may befrom 20 Hz to 25 Hz, which a range shown to be effective to treaturinary and/or bowel incontinence with tibial nerve stimulation. Thegenerated stimulation signal may have a stimulation pulse width in arange of between 300 μs and 100 μs, 290 μs and 110 μs, 280 μs and 120μs, 270 μs and 130 μs, 260 μs and 140 μs, 250 μs and 150 μs, 240 μs and160 μs, 230 μs and 170 μs, 220 μs and 180 μs, or 210 μs and 190 μs. Forexample, a pulse pattern with 200 μs pulses at 20 Hz may be shownbecause this pattern has been shown effective for to treat urinaryand/or bowel incontinence with tibial nerve stimulation.

In other embodiments, the circuitry may be configured to generatedifferent pulse patterns for different indications. The stimulationpulse patterns may be from 90 to 500 μs at 20 to 100 Hz, which have beenshown effective for relief from peripheral nerve pain. For peripheralnerve field stimulation, most patients prefer the frequency to bebetween 20 and 50 Hz. Anything higher than this range may be felt as avery strong sensation, or cause burning or pinching. Pulse width in therange of 90 to 250 μs may be best tolerated. Stimulation at higherfrequencies, e.g. 1200 Hz, have also been shown effective for relieffrom peripheral nerve pain and may have an additional advantage of notprovoking a sensory response in the patient. The circuitry may beconfigured to generate stimulation signals at these higher frequencies.

The implant may be powered in many ways. The battery may comprise aprimary battery. The capacity of the primary battery may be in a rangebetween 360 mAH and 100 mA, 350 mAH and 110 mAH, 340 mAH and 120 mAH,330 mAH and 130 mAH, 320 mAH and 140 mAH, 310 mAH and 150 mAH, 300 mAHand 160 mAH, 290 mAH and 170 mAH, 280 mAH and 180 mAH, 270 mAH and 190mAH, 260 mAH and 200 mAH, 250 mAH and 210 mAH, or 240 mAH and 220 mAH,to name a few. The circuitry of the implantable device may have a lowcurrent drain such that the primary battery may be effective for manyyears. The battery of the implant may be rechargeable and may berecharged wirelessly. The recharging power may be furnished from anexternal (non-implanted) device during a charging period. The implantmay have no battery, with power furnished from an external(non-implanted) device when stimulation is required.

The implant may have a size and/or shape such that it is implanted inthe body of the subject with minimal long-term discomfort. For example,the total volume of the implant is in a range between 1.9 cc and 0.1 cc,1.8 cc and 0.2 cc, 1.7 cc and 0.3 cc, 1.6 cc and 0.4 cc, 1.5 cc and 0.5cc, 1.4 cc and 0.6 cc, 1.3 cc and 0.7 cc, 1.2 cc and 0.8 cc, or 1.1 ccand 0.9 cc. The enclosure may be hermetically sealed. The enclosure maybe cylindrical, tubular, or rectangular (e.g., as in a pill box). Theenclosure may comprise an insulative outer coating to prevent undesiredstimulation of tissue such as muscle. The insulative outer coating maycomprise one or more of silicone rubber, parylene, polyurethane, PEEK,PTFE, or ETFE.

In exemplary embodiments, the implant has a longevity exceeding 5 yearsin a 1.0 cc volume and is suitable for implantation near the posteriortibial nerve. For example, the enclosure or housing of the implant maybe 7 mm in diameter and 25 mm long. In addition to being suitable totreat urinary and/or bowel incontinence, the device design and formfactor may be appropriate for other therapies for which intermittentstimulation has been demonstrated effective: Such therapies include, butare not limited to: (a) intermittent sphenopalatine ganglion stimulation(SPGS) for headaches; (b) bilateral supraorbital nerve stimulation(SNSt) for headaches at 20 minutes per day; (c) vagus nerve stimulationfor epilepsy and depression at 30 seconds every 5 minutes; (d) PTNS forpelvic pain; and, (e) stimulation in the infraorbital foramina forneuropathic pain.

The electrode assembly may be separated from the enclosure by the leadby a distance in a range between 15 cm and 0.1 mm, 14 cm and 0.1 mm, 13cm and 0.1 mm, 12 cm and 0.1 mm, 11 cm and 0.1 mm, 10 cm and 0.1 mm, 9cm and 0.1 mm, 8 cm and 0.1 mm, 7 cm and 0.1 mm, 6 cm and 0.1 mm, 5 cmand 0.1 mm, 4 cm and 0.1 mm, 3 cm and 0.1 mm, 2 cm and 0.1 mm, or 1 cmand 0.1 mm. At least a portion of the lead may be insulated.

One or more of the electrode assembly or enclosure may comprise afixation element to anchor into the tissue, thereby reducing migrationof the implantable device during long-term use in the subject. Thefixation element may comprise a hook, a pin, a screw, a pigtail screw, aring, a grasper, a suture, a tine, or a cuff, to name a few examples.

The electrode assembly may be configured for permanent placementadjacent the tissue. At least a portion of the electrode assembly may beconfigured for placement adjacent a nerve of the subject. The electrodeassembly may comprise an insulative assembly body (e.g., to minimizeundesired stimulation to undesired tissue such as muscle where the bodymay be implanted) and at least one electrode. The electrode(s) maycomprise a unipolar electrode, bipolar electrodes, or tripolarelectrodes.

The pulse generator at the housing or enclosure of the implant may beconnected to the lead in many ways. One or more of the lead or theelectrode assembly comprises a connector removably coupling theelectrode assembly to the lead or the enclosure. In some embodiments,the lead does not have a connector detachable from the pulse generator,but instead connects permanently to the pulse generator, simplifyingconstruction and improving reliability. In some embodiments, the leadhas a connector detachable from the pulse generator. This detachabilitycan allow the user to implant the lead for a qualification period, andthen, if qualification is successful, to implant a pulse generator andconnect it to the previously-implanted lead. The detachability also canfacilitate implantation with a single incision, where the pulsegenerator is implanted cranial to the incision, and the lead isimplanted caudal to the incision. In some embodiments, the leadcomprises an inductor configured to act as an RF trap. In someembodiments, the electrode assembly comprises a return electrodedisposed on or integral with the enclosure.

The circuitry may comprise a wireless communication transceiverconfigured to wirelessly communicate with an external programmer. Thewireless communication transceiver of the circuitry may be configured toreceive instructions from the external programmer to one or more ofactivate, schedule, modify, modulate, monitor, or end a therapeuticprotocol. The wireless communication transceiver may communicate withthe external programmer through one or more a Bluetooth connection, aBluetooth LE connection, a Zigbee connection, a Wi-Fi connection, an IRconnection, an RF connection, an ultrasound-based connection, a WiMaxconnection, an ISM connection, an AM connection, an FM connection, aconductive connection, or a magnetic connection. The wirelesscommunication transceiver of the circuitry may communicate with theexternal programmer through a conductive connection. The wirelesscommunication transceiver may be configured to generate a communicationsignal received by the external programmer, the communication signalbeing one or more of below a threshold stimulation pulse amplitude,below a threshold stimulation pulse duration, or during a refractoryperiod of a nerve.

The external programmer may comprise one or more of a key fob, asmartphone, a smartwatch, a tablet computer, a laptop computer, awearable computing device, a wand, a strap configured to at leastpartially encircle a limb of the subject, or other portable computingdevice. The external programmer may be in communication with a printingdevice to record a therapeutic protocol delivered by the implantabledevice.

The external programmer may comprise a wearable magnetic fieldgenerator. The wearable magnetic field generator may be aligned with theimplantable device to optimize magnetic communication with the wirelesscommunication transceiver of the implantable device when worn.

The external device may comprise a tissue stimulator. The tissuestimulator may comprise one or more of a percutaneous tibial nervestimulator or a transcutaneous electrical nerve stimulator. The wirelesscommunication transceiver may be configured to communicate to theexternal programmer one or more of a current status of the battery, avoltage status of the battery, time, a therapy status, a waveform of thegenerated stimulation signal, a device orientation, a device alignment,or other implantable device information or command.

The implantable device may be configured to detect a magnetic field. Thegeneration of the stimulation signal may be postponed, disabled, orotherwise modified in response to the detected magnetic field. Themagnetic field may be generated from an external programmer tocommunicate with the circuitry of the implantable device. The magneticfield may be detected with a magnetic field sensor such as a giantmagnetoresistance (GMR) switch, which is small, light, and reliable. Themagnetic field comprises an MRI field. For example, when an MRI field isdetected, the implant or at least the stimulation signals generated maybe switched off. More typically, the magnetic field sensor may detectsignals from the external programmer such as to receive instructions. Inaddition, the patient or medical professional can apply a permanentmagnet in vicinity of the implanted pulse generator, for postponing,modifying, or stopping therapy; for example if therapy becomesunpleasant or ineffective.

The implantable device may further comprise an accelerometer coupled tothe circuitry. The accelerometer may be configured to detect anorientation or alignment of the implantable device or a movement of thesubject. The circuitry may be configured to disable, postpone, orotherwise modify a therapeutic protocol of the implantable device inresponse to the detected orientation, alignment, or movement.

While the present disclosure describes neuromodulation for overactivebladder (OAB) or bowel incontinence (BI) at a branch of the sciaticnerve and more particularly the posterior tibial nerve, the implantabledevice may be suitable to stimulate many other tissues and treat manyother conditions. Alternatively or in combination for OAB or BI, theimplantable device may more particularly target a sural nerve, pudendalnerve, or superficial peroneal nerve, all of which are branches of thesciatic nerve. An advantage to targeting these target nerves or branchesmay include ease of access. The implantable device may also provideclinical utility for treatment of acute pain, chronic pain,hypertension, congestive heart failure, gastro-esophageal reflux,obesity, erectile dysfunction, insomnia, a movement disorder, or apsychological disorder. In particular for treatment of peripheral nervepain, the implantable device could target one or more of the following:greater occipital nerve, tibial nerve, superficial peroneal nerve,saphenous nerve, Intercostal nerve, or other peripheral nerve of thesubject. Another application of the implantable device may bestimulating the ileo-inguinal nerve for pain following hernia surgery,or the genitofemoral nerve for relief of post-vasectomy pain, which isan untreated problem in tens of thousands of patients. Some IC(interstitial cystitis) patients with pelvic pain may also be responsiveto PTNS.

In other examples, the electrode assembly may be configured to directthe generated stimulation signal to one or more of a greater occipitalnerve, a tibial nerve, a superficial peroneal nerve, a saphenous nerve,an intercostal nerve, a subcostal nerve, a lumbar plexus, a sacralplexus, a femoral nerve, a pudendal nerve, a sciatic nerve, a femoralnerve, a deep peroneal nerve, a common peroneal nerve, an ulnar nerve,an obturator nerve, a genitofemoral nerve, an iliohypogastric nerve, amedian nerve, a radial nerve, a musculocutaneous nerve, a brachialplexus, or other peripheral nerve of the subject. The generatedstimulation signal may be configured to treat one or more of urinaryincontinence, bowel incontinence, acute pain, chronic pain,hypertension, congestive heart failure, gastro-esophageal reflux,obesity, erectile dysfunction, insomnia, a movement disorder, or apsychological disorder.

Aspects of the present disclosure may also provide methods forstimulating tissue with an implant permanently implanted in a body of asubject for long-term use. The implant may comprise the implantdescribed above and herein. The implant implanted in a body of a subjectmay be powered with a battery. The battery may be enclosed in anenclosure of the implant. The implant may have a low background currentdrain between 0.1 μA and 5 μA from the primary battery. A stimulationsignal may be generated with circuitry enclosed in the enclosure. Thecircuitry may generate the stimulation signal with a low duty cycle ofbetween 0.1% and 2.5%, or other low duty cycles or current drains. Thestimulation signal may be directed to tissue of the subject with anelectrode array at least partially separated from the enclosure of theimplant by a lead coupling the electrode array with the circuitry withinthe enclosure. As described above and herein, the low duty cycle and lowcurrent drain of the generated stimulation pulse combine to provide auseful life of the implantable device implanted in the body of at least5 years without removal from the body. The implant may be used in manyways, configured in many ways, and include a variety of features asdescribed above and herein.

Aspects of the present disclosure may also provide methods for improvinga urinary or bowel function in a subject. An incision may be created ina leg of a patient. A first tunnel may be created in the leg of thepatient through the incision. A second tunnel may be created in the legof the patient through the incision. One or more of the first or secondtunnels may be created with a blunt dissection tool as described aboveand herein. An implantable pulse generator may be placed in the firsttunnel. At least a portion of an electrode assembly may be placed in thesecond tunnel so that the electrode assembly is positioned at oradjacent a sciatic nerve or a branch thereof such as by at leastpartially encircling the sciatic nerve or branch thereof with a cuff ofthe electrode assembly. The implantable pulse generator and theelectrode assembly may be coupled to one another. Together, theimplantable pulse generator and the electrode assembly may comprise animplant or implantable device as described above and herein. One or moreof the implantable pulse generator or the electrode assembly may befixated to the first or second tunnel, respectively, such as byanchoring a fixation element of the implantable pulse generator or theelectrode assembly to the first or second tunnels, respectively. Theincision may be closed. The implantable pulse generator may generate astimulation signal and the electrode assembly may direct the stimulationsignal to the tissue of the subject. The stimulation signal may improvethe urinary or bowel function in the subject. As described above andherein, the implantable pulse generator may generate a stimulationsignal with a low duty cycle of between 0.1% and 2.5% and a lowbackground current drain of between 0.1 μA and 5 μA, or other low dutycycles and/or low current drains. As described above and herein, theimplantable pulse generator and the electrode assembly may be implantedin the body for at least 5 years without removal from the body or losingfunction.

Aspects of the present disclosure may also provide methods for improvinga urinary or bowel function in a subject. A primary incision may becreated in a leg of a patient. A secondary incision may be created inthe leg of the patient. A tunnel between the first and second incisionsmay be created in the leg of the patient. The tunnel may be created witha blunt dissection tool as described above and herein. A pulse generatorof an implant may be advanced through the primary incision to bepositioned at or near the stimulation site. At least a portion of anelectrode assembly of the implant may be advanced through the secondaryincision to be positioned at or adjacent a sciatic nerve or a branchthereof such as by at least partially encircling the sciatic nerve orbranch thereof with a cuff of the electrode assembly. The pulsegenerator and the portion of the electrode assembly may be coupled toone another through a lead positioned in the tunnel. The implant may befixated through one or more of the primary or secondary incisions suchas by anchoring a fixation element of the implantable pulse generator orthe electrode assembly to the first or second tunnels. The primary andsecondary incisions may be closed. The electrode assembly of the implantmay direct a stimulation signal to the tissue of the subject. Thestimulation signal may improve the urinary or bowel function in thesubject. As described above and herein, the implantable pulse generatormay generate a stimulation signal with a low duty cycle of between 0.1%and 2.5% and a low background current drain of between 0.1 μA and 5 μA,or other low duty cycles and/or low current drains. As described aboveand herein, the implantable pulse generator and the electrode assemblymay be implanted in the body for at least 5 years without removal fromthe body or losing function.

Aspects of the present disclosure provide system for stimulating tissue.An exemplary system may comprise an implantable pulse generator, anelectrode assembly, and an external programmer. The implantable pulsegenerator may be configured to be implanted in a patient. Theimplantable pulse generator may comprise circuitry to generate astimulation signal and receive a wireless signal. The electrode assemblymay be configured to be implanted in the patient. The electrode assemblymay be configured to direct the stimulation signal generated by theimplantable pulse generator to tissue of the patient. The externalprogrammer may be configured to generate the wireless signal received bythe implantable pulse generator. The stimulation signal may be generatedby the implantable pulse generator in response to the wireless signal.As described above and herein, the implantable pulse generator maygenerate a stimulation signal with a low duty cycle of between 0.1% and2.5% and a low background current drain of between 0.1 μA and 5 μA, orother low duty cycles and/or low current drains. As described above andherein, the implantable pulse generator and the electrode assembly maybe implanted in the body for at least 5 years without removal from thebody or losing function.

In many embodiments, the implantable pulse generator may comprise aprimary battery. In other embodiments, an external power source may beneeded. The system may further comprise an external power sourceconfigured to wirelessly provide power to the implantable pulsegenerator. The external power source may provide power to theimplantable pulse generator magnetically, inductively, ultrasonically,or with RF power transmission. The external power source may beconfigured to wirelessly recharge a rechargeable power cell of theimplantable pulse generator. The external programmer may comprise theexternal power source.

The external programmer (e.g., the “wand”) may comprise a relayconfigured to receive a first signal from a separate control device andtransmit the wireless signal to the implantable pulse generator inresponse to the received first signal. The separate control device maybe user operated for display and control. The separate control devicemay comprise one or more of a key fob, a smartphone, a smartwatch, atablet computer, a laptop computer, a wearable computing device, orother portable computing device. The separate control device maycomprise a wearable magnetic field generator. The wearable magneticfield generator may be aligned to optimize magnetic communication with awireless communication transceiver of the implantable pulse generatorwhen worn. In some embodiments, the user or subject may choose betweenusing only the relay, the separate control device, or both. Forinstance, the relay may include controls and a display to interface withthe implant.

The external programmer or relay may be in communication with theseparate control device and the external programmer or relay may be incommunication with the implantable device through one or more of aBluetooth connection, a Bluetooth LE connection, a Zigbee connection, aWi-Fi connection, an IR connection, an RF connection, anultrasound-based connection, a WiMax connection, an ISM connection, anAM connection, an FM connection, a conductive or a magnetic connection.For instance, the wireless communication transceiver of the circuitrymay communicate with the external programmer through a conductiveconnection, and the wireless communication transceiver may be configuredto generate a communication signal received by the external programmer.These conductive communications signals may be generated by the pulsegenerator so as not to stimulate any nerve, muscle, or other tissue. Thecommunication signal may be one or more of below a threshold stimulationpulse amplitude, below a threshold stimulation pulse duration, or duringa refractory period of a nerve. Generally, the communication between therelay and the separate control device may be relatively high power andthe communication between the implant and the relay may be relative lowpower and short range. Accordingly, the separate control device may beplaced in a convenient location with the user while not compromising thelow power requirements of the implant.

In some embodiments, the implantable device communicates directly withthe external programmer without any relay. The external programmer maycomprise one or more of a key fob, a smartphone, a smartwatch, a tabletcomputer, a laptop computer, a wearable computing device, a strapconfigured to at least partially encircle a limb of the subject, orother portable computing device. The external programmer may comprise ageneral use computing device (e.g., a tablet computer) having softwaretherein to communicate with the implant. Alternatively or incombination, the external programmer or wand may itself include controlsand displays, such that another computing device may not be necessary.

In some embodiments, the external programmer is in communication with aprinting device to record a therapeutic protocol delivered by theimplantable device.

In some embodiments, the external device comprises a tissue stimulator.The tissue stimulator may be configured to deliver a signal to thetissue of the subject through a percutaneously or transcutaneouslyimplanted needle or electrode. The needle or electrode may be implantedtemporarily such as to qualify the subject or patient for the system.The subject or patient may be qualified for use of the system in manyways for a variety of reasons as described above and herein.

The external programmer may be configured to receive one or more of acurrent status of the battery, a voltage status of the battery, time, atherapy status, a waveform of the generated stimulation signal, a deviceorientation, a device alignment, or other implantable device informationor command.

The external programmer may comprise an easy to use user interface. Forexample, the external programmer may comprise a single control buttonand the external programmer may be operable from the single controlbutton. The external programmer may be differently responsive to asingle short press of the single control button, a double short press ofthe single control button, and a hold of the single control button. Insome embodiments, the external programmer may comprise a display orindicator light which, for example, indicates an active wirelessconnection between the external programmer and the implantable pulsegenerator. The wireless signal received by the implantable pulsegenerator may be configured to one or more of activate, schedule,postpone, modify, modulate, monitor, or end a therapeutic protocol.

INCORPORATION BY REFERENCE

All publications, patents, and patent applications mentioned in thisspecification are herein incorporated by reference to the same extent asif each individual publication, patent, or patent application wasspecifically and individually indicated to be incorporated by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the invention are set forth with particularity inthe appended claims. A better understanding of the features andadvantages of the present invention will be obtained by reference to thefollowing detailed description that sets forth illustrative embodiments,in which the principles of the invention are utilized, and theaccompanying drawings of which:

FIG. 1 shows a side view of a bipolar miniature implantedneurostimulator having a cuff electrode assembly, according to manyembodiments;

FIG. 2 shows a side view of a unipolar miniature implantedneurostimulator having a cuff electrode assembly, according to manyembodiments;

FIG. 3 shows a side view of a unipolar miniature implantedneurostimulator with an RF trap and a rod electrode assembly, accordingto many embodiments;

FIG. 4 shows a side view of a bipolar miniature implantedneurostimulator with an RF trap and a rod electrode assembly, accordingto many embodiments;

FIG. 5 shows a perspective view of a lower leg of a subject having atunnel made therein for the implantation of a miniature implantedneurostimulator, according to many embodiments;

FIG. 6 shows a side view of a blunt dissection tool, according to manyembodiments;

FIG. 7 shows a block diagram for a miniature implanted neurostimulatorwith inductive telemetry, according to many embodiments;

FIG. 8 shows a block diagram for a miniature implanted neurostimulatorwith radiofrequency (RF) telemetry, according to many embodiments;

FIG. 9 shows a block diagram of an application specific integratedcircuit (ASIC) usable for miniature implanted neurostimulators,according to many embodiments;

FIG. 10 shows a wearable programmer or limb wand for miniature implantedneurostimulators, according to many embodiments;

FIG. 11 shows another wearable programmer or limb wand for miniatureimplanted neurostimulators, according to many embodiments;

FIG. 12 shows a wearable programmer or limb wand having onboardcontrol(s) and display(s), according to many embodiments;

FIG. 13 shows another wearable programmer having onboard control(s) anddisplay(s), according to many embodiments;

FIG. 14 shows a block diagram for the components of a wearableprogrammer or limb wand having an onboard (percutaneous tibialneurostimulation) PTNS generator, according to many embodiments;

FIG. 15 shows a block diagram for the components of a wearableprogrammer or limb wand, according to many embodiments;

FIG. 16 shows a state diagram for a low duty-cycle stimulator with ascheduled therapy, according to many embodiments;

FIG. 17 shows a state diagram for a low duty-cycle stimulator withdeferred therapy, according to many embodiments;

FIG. 18 shows a front view of a patient operated key fob programmer,according to many embodiments;

FIG. 19 shows a block diagram for the patient operated key fob of FIG.18 ;

FIG. 20 shows a schematic of a key fob programmer for miniatureimplanted neurostimulators, according to many embodiments;

FIG. 21 shows a schematic of a smartphone programmer system forminiature implanted neurostimulators, according to many embodiments;

FIG. 22 shows a perspective view of a lower leg of a subject having atunnel made therein for the implantation of a miniature implantedneurostimulator, according to many embodiments;

FIG. 23 shows a side view of a miniature implanted neurostimulatorhaving an anchor to prevent migration, according to many embodiments;

FIG. 24 shows a perspective view of a lower leg of a subject having twotunnels made therein for the implantation of a miniature implantedneurostimulator, according to many embodiments;

FIG. 25 shows a block diagram of a miniature implanted neurostimulatorwith hybrid telemetry, according to many embodiments;

FIG. 26 shows a schematic of a programmer-to-implant telemetry scheme,according to many embodiments;

FIG. 27 shows a schematic of an implant-to-programmer telemetry scheme,according to many embodiments;

FIG. 28 shows a graph of implant marker synchronization pulses whenthere no link established, according to many embodiments;

FIG. 29 shows a graph of implant marker synchronization pulses whenthere is a link established, according to many embodiments;

FIG. 30 shows a graph of implant marker synchronization pulses duringstimulation, accordingly to many embodiments;

FIG. 31 shows a graph of exemplary implant-to-programmer communicationdata, according to many embodiments;

FIG. 32 shows a graph of exemplary implant-to-programmer communicationdata, according to many embodiments;

FIG. 33 shows a graph of exemplary programmer-to-implant data, accordingto many embodiments;

FIG. 34 shows a graph of programmer-to-implant data example duringstimulation, according to many embodiments;

FIG. 35 shows a graph of a telemetry data format, according to manyembodiments; and

FIG. 36 shows a block diagram of an external programmer, according tomany embodiments.

DETAILED DESCRIPTION

To provide further clarity to the Detailed Description and associatedFigures, the following list of components and associated referencenumbers is provided. Like reference numbers refer to like elements.

FIG. 1

-   -   1—miniature implanted neurostimulator    -   2—anchor feature    -   3—cell compartment    -   4—electronics compartment    -   5—header    -   6—flexible insulated lead wires    -   7—bipolar cuff electrode assembly    -   8—proximal cuff electrode    -   9—distal cuff electrode

FIG. 2

-   -   1—miniature implanted neurostimulator    -   2—anchor feature    -   3—cell compartment    -   4—electronics compartment    -   5—header    -   6—flexible insulated lead wire    -   10—unipolar cuff electrode assembly    -   11—distal cuff electrode

FIG. 3

-   -   1—miniature implanted neurostimulator    -   2—anchor feature    -   3—cell compartment    -   4—electronics compartment    -   5—header    -   6—flexible insulated lead wire    -   12—rod electrode assembly    -   13—distal rod electrode    -   14—inductor

FIG. 4

-   -   1—miniature implanted neurostimulator    -   2—anchor feature    -   3—cell compartment    -   4—electronics compartment    -   5—header    -   6—flexible insulated lead wire    -   14—inductor    -   15—bipolar rod electrode assembly    -   16—proximal rod electrode    -   17—distal rod electrode

FIG. 5

-   -   20—single incision surgical procedure    -   21—stimulation site    -   22—incision    -   23—tunnel for generator    -   24—tunnel for electrode assembly    -   25—leg    -   26—nerve

FIG. 6

-   -   30—blunt dissection tool    -   31—rod    -   32—handle

FIG. 7

-   -   35—block diagram, miniature implanted neurostimulator with        inductive telemetry    -   36—cell    -   37—ASIC    -   38—telemetry coil    -   39—DC blocking capacitor    -   40—hermetic feedthrough    -   41—TIP (cathodic stimulator output)    -   42—RING (anodic stimulator output)

FIG. 8

-   -   45—block diagram, miniature implanted neurostimulator with RF        telemetry    -   36—cell    -   37—ASIC    -   39—DC-blocking capacitor    -   40—hermetic feedthrough    -   41—TIP (cathodic stimulator output)    -   42—RING (anodic stimulator output)    -   43—RF coupling capacitor

FIG. 9

-   -   50—block diagram, miniature implanted neurostimulator ASIC    -   51—Q, V monitor    -   52—regulator    -   53—charge pump    -   54—processor    -   55—stimulator output    -   56—32 kHz oscillator    -   57—fast oscillator    -   58—implant telemetry    -   59—32 kHz external crystal    -   60—charge pump capacitor    -   61—charge pump capacitor    -   62—stimulator output    -   63—telemetry inductor

FIG. 10

-   -   65—limb wand    -   66—wand main housing    -   67—flexible strap

FIG. 11

-   -   70—limb wand    -   71—wand main housing

FIG. 12

-   -   75—torso programmer    -   76—programmer main housing    -   77—keyboard and display unit    -   78—flexible strap

FIG. 13

-   -   80—programmer with integrated PTNS stimulator    -   81—optional telemetry wand connection    -   82—TIP (cathodic stimulator output)    -   83—RING (anodic stimulator output)    -   84—keyboard and display unit

FIG. 14

-   -   85—block diagram of programmer with integrated PTNS stimulator    -   86—power supply    -   87—charge pump    -   88—V monitor    -   89—stimulator output    -   90—processor    -   91—oscillator    -   92—real time clock    -   93—implant telemetry    -   94—keyboard and display I/O    -   95—battery    -   96—on/off switch    -   97—charge pump capacitor    -   98—charge pump capacitor    -   99—DC-blocking capacitor    -   100—TIP connection    -   101—RING connection    -   102—telemetry inductor    -   103—display LED    -   104—key switch

FIG. 15

-   -   110—block diagram, limb wand    -   111—power supply    -   112—V monitor    -   113—processor    -   114—RF telemetry    -   115—implant telemetry    -   116—oscillator    -   117—keyboard and display I/O    -   118—battery    -   119—on/off switch    -   120—RF antenna    -   121—telemetry inductor    -   122—display LED    -   123—key switch

FIG. 16

-   -   125—low duty cycle stimulator state diagram    -   126—IDLE state    -   127—enable stimulator output state    -   128—transition occurring every week    -   129—transition occurring after 30 minutes

FIG. 17

-   -   130—low duty cycle stimulator with deferred therapy    -   131—IDLE state    -   132—enable stimulator output state    -   133—1-hour delay state    -   134—transition occurring every week    -   135—transition occurring after 30 minutes of stimulation    -   136—transition occurring after 1-hour delay    -   137—transition occurring after leg movement detected

FIG. 18

-   -   140—patient key fob    -   141—key fob housing    -   142—LED indicating key fob is active    -   143—LED indicating low battery status    -   144—key to activate key fob

FIG. 19

-   -   150—block diagram, patient key fob    -   151—power supply    -   152—V monitor    -   153—processor    -   154—RF telemetry    -   155—oscillator    -   156—display driver    -   157—battery    -   158—key switch    -   159—RF antenna    -   160—display LED

FIG. 20

-   -   165—smart phone key fob/programmer system via direct implant        connection    -   166—human leg    -   167—miniature implanted neurostimulator    -   168—key fob app/programmer app running on smart phone

FIG. 21

-   -   170—smart phone programmer system via indirect implant        connection    -   171—human leg    -   172—miniature implanted neurostimulator    -   173—programmer app running on smart phone    -   174—limb wand

FIG. 22

-   -   180—single incision surgical procedure    -   181—leg    -   182—incision    -   183—tunnel for generator    -   184—nerve    -   185—stimulation site

FIG. 23

-   -   190—miniature implanted neurostimulator with alternative anchor    -   191—miniature implanted neurostimulator    -   192—anchor    -   193—flexible insulated lead wire    -   194—electrode assembly

FIG. 24

-   -   195—double incision surgical procedure    -   196—leg    -   197—secondary incision    -   198—primary incision    -   199—stimulation site    -   200—nerve

FIG. 25

-   -   210—miniature implanted neurostimulator with hybrid telemetry    -   211—cell    -   212—microprocessor    -   213—giant magnetoresistance sensor    -   214—voltage converter/charger    -   215—supply filter capacitor    -   216—inductor    -   217—flyback diode    -   218—stimulation tank capacitor    -   219—charge balancing resistor    -   220—input protection diode    -   221—charge balancing capacitor    -   222—stimulation pulse MOSFET    -   223—attenuator    -   224—attenuator    -   225—attenuator    -   226—32768 Hz crystal    -   227—hermetic feedthrough    -   228—RING connection    -   229—TIP connection    -   275—pull-up resistor

FIG. 26

-   -   230—programmer-to-implant telemetry scheme    -   231—programmer transmit switch    -   232—snubber diode    -   233—electromagnet    -   234—skin barrier    -   235—giant magnetoresistance sensor

FIG. 27

-   -   240—implant-to-programmer telemetry scheme    -   241—miniature implanted neurostimulator    -   242—skin barrier    -   243—programmer skin electrodes    -   244—amplifier/filter    -   245—detector

FIG. 36

-   -   250—block diagram, programmer    -   251—battery    -   252—on/off switch    -   253—power supply    -   254—voltage monitor    -   255—microprocessor    -   256—oscillator    -   257—keyboard and display I/O    -   258—detector    -   259—amplifier/filter    -   260—electromagnet    -   261—snubber diode    -   262—programmer transmit switch    -   263—display LED    -   264—key switch    -   265—skin electrodes

I. Miniature Implanted Neurostimulator

An exemplary miniature implanted neurostimulator is shown in FIG. 1 .The generator portion may be packaged in a cylindrical form, typically1.0 cc in volume or less and no more than 6 to 7 mm in diameter. Thegenerator (1) may comprise a primary cell (3), typically lithium CFxchemistry, an electronics compartment (4), an anchor (2), and a header(5). The outer shell is typically made from medical grade titanium orstainless steel, and the enclosure is typically hermetic. Theelectronics compartment (4) may contain a hermetic feedthrough (notshown) to allow the cathodic (TIP) connection to pass through the header(5). The outer surface of the enclosure may be electrically connected tothe anodic connection (RING). The header is typically made from medicalgrade epoxy, PEEK, or one or more other medical grade biocompatiblepolymers.

Flexible insulated lead wires (6) may connect the header (5) to thebipolar cuff electrode assembly (7). The flexible insulated lead wiresare typically insulated with silicone rubber or polyurethane. Theconductive wire material is typically MP35N and constructed as amulti-strand cable or multi-filar coil design for flexural strength. Thebipolar cuff material is typically silicone rubber or polyurethane andthe electrodes (8) and (9) are made from platinum or platinum iridium.The cuff electrode assembly encircles the nerve to stimulate. In thisembodiment, the outer generator enclosure is coated with either siliconerubber, polyurethane, or Parylene. The outer enclosure (anode) may beelectrically connected to the proximal cuff electrode (8) while thefeedthrough connection (cathode) may connect to the distal cuffelectrode (9). This configuration can prevent stimulating muscleadjacent to the outer enclosure.

The anchor feature (2) shown in FIGS. 1 through 4 is used to suture thestimulator to tissue or bone to prevent migration of the implantedneurostimulator.

In some embodiments, a unipolar cuff electrode assembly may be used asshown in FIG. 2 . The cuff electrode assembly (10) may contain only onedistal electrode (11) connected to the cathodic connection (TIP). Thiselectrode may be connected via a flexible insulated lead wire (6) to thefeedthrough (not shown) through an insulating header (5). The outerenclosure of the generator (1) is typically not coated and can thereforeserve as the anodic electrode (RING).

In some embodiments, a unipolar rod electrode assembly (12) may be usedas shown in FIG. 3 . This electrode configuration may be placed adjacentto the intended nerve. The unipolar electrode assembly body is typicallymade from silicone rubber or polyurethane and the electrode made fromplatinum or platinum iridium. The generator (1) shown in FIG. 3 issimilar to the generator (1) shown in FIG. 1 . The outer enclosure maybe un coated and can serve as the anodic (RING) electrode. The cathodicconnection (TIP) may pass through the feedthrough (not shown), throughan insulating header (5), may connect to the flexible insulated leadwire (6), and may ultimately connect to the distal electrode (13) bypassing through an inductor (14). The inductor can serve as an RF trapfor configurations where the telemetry scheme is RF rather thaninductive. With RF telemetry, the RF energy may exit the electronicenclosure (4) via the same single feedthrough (not shown) used for theTIP connection. This can allow the proximal part of the lead wire toalso act as an antenna while the inductor (14) prevents RF energy fromreaching the distal electrode (13), preventing unintended current flow.If inductive telemetry is used, inductor (14) may not be required.

In the embodiments shown by FIGS. 1 to 3 , the flexible insulated leadwire(s) are, for example, 2 to 4 cm in length, and can allow the distalelectrode to be placed at the stimulated nerve site while allowing thegenerator to be located in comfortable position for the patient.

In some embodiment, a bipolar rod electrode assembly may be used asshown in FIG. 4 . The electrode assembly (15) may contain twoelectrodes, a proximal electrode (16) connected to the anodic connection(RING) and a distal electrode (17) connected to the cathodic connection(TIP). The can may be coated and the flexible lead wire assembly maycontain at least two insulated wires for the anodic and cathodicconnections.

Although rod shaped electrodes are shown in FIGS. 3 and 4 for theelectrode assembly, the shape of the electrode assembly may take onother forms to optimize one or more of the following: performance of theelectrode, mechanical stability of the electrode, comfort, and ease ofinstallation.

In the embodiments for the unipolar (FIG. 3 ) and bipolar (FIG. 4 ) rodelectrode assembly, the preferred surgical procedure may create only oneincision or puncture wound at the leg entry point and a blunt dissectingtool may be used to create a tunnel from the wound to the stimulationsite. A pictorial diagram for this procedure is shown in FIG. 5 . Asmall incision or puncture wound (22) may first be created in the leg.Then, a blunt dissection tool similar in diameter to the electrodediameter may be used to dissect a path for the electrode and flexibleinsulated wires (24). This tunnel may be made from the wound (22) to theintended stimulation site (21) adjacent to the nerve (26). Then, alarger dissection tool may be introduced into the same tunnel but onlyinserted a sufficient length to accommodate the miniature implantedneurostimulator body (23) as shown in FIG. 5 . An example of the bluntdissection tool (30) is shown in FIG. 6 . Each blunt dissection tool(30) may be made, for example, from a stainless steel rod (31) with thedistal end shaped with a ball nose (radius of the tip equal to the 1%the diameter) and a plastic handle (32) on the other end. The rod maybe, for example, malleable to create a curved path. It may also bepreferred that the rod be visible under fluoroscopy to help position thedistal electrode at the intended stimulation site, although ultrasoundor other imaging is also foreseen. The incision site may then be closed.

An exemplary alternative surgical procedure that may require only oneincision is shown in FIG. 22 . A small incision or puncture wound (182)may first be created in the leg. The incision may exposes thestimulation site (185) allowing for any of the electrode assemblyembodiments to be placed next to the nerve (184). Using a bluntdissection tool (30), a tunnel can be created for the miniatureimplanted neurostimulator (183). To prevent migration of the generator,a different anchoring method may be used for this alternative procedure.FIG. 23 shows a miniature implanted neurostimulator with an alternativeanchor (190). The anchor (192) may be constructed from silicone rubberand can allow the generator to be placed in the tunnel (183) shown inFIG. 22 . The anchor (192) of FIG. 23 can prevent device migration. Theincision site can then be closed.

An exemplary alternate surgical procedure that may require two incisionsis shown in FIG. 24 . A primary incision or puncture wound (198) mayfirst be created in the leg. The incision may expose the stimulationsite (199) allowing for any of the electrode assembly embodiments to beplaced next to the nerve (200). A secondary incision or puncture wound(197) may be created. Using a blunt dissection tool (30), a tunnel maybe created between the two incision sites. The miniature implantedneurostimulator may then be inserted in the tunnel and the anchormechanism (2) as shown in FIGS. 1 through 4 may be sutured in place viaaccess from the secondary incision (197). Both incision sites may thenbe closed.

FIG. 7 shows a block diagram for the miniature implanted neurostimulatorwith inductive telemetry (35). The miniature implanted neurostimulatorwill typically be powered by a primary cell (36). This cell is typicallylithium CFx but other chemistries are possible. A primary cell may bepreferred due to the simplicity of the design, patient freedom fromrecharging, and high energy density. With a cell volume of approximately0.75 cc, a cell capacity of approximately 230 mAH, for example, can beobtained with a lithium primary cell.

Connected to the cell (36) may be a mixed signal ASIC (37). This ASIC istypically designed and fabricated using standard CMOS processes and cancontain both digital and analog circuitry. Connected to the ASIC may bea small inductor (38) to provide bidirectional inductive telemetry witha programmer. The stimulator output is also shown exiting the ASIC andmay be connected to a DC-blocking capacitor (39). This capacitor canensure that a charge-balanced waveform is applied to the stimulatingelectrode, thus avoiding electrode corrosion issues.

The DC-blocking capacitor (39) may connect through a hermeticfeedthrough (40) to the TIP (41) connection (cathodic stimulatoroutput). The hermetic feedthrough can protect the electronicscompartment from the corrosive environment of the body. In preferredembodiments, a CFx cell (36) may be utilized. The cell housing may bemade from titanium and can serve as the cell negative connection. Asshown in FIG. 7 , the cell negative connection may connect to the outerhousing of the cell and can serve as the RING connection (anodicstimulator output) (42).

FIG. 8 shows a block diagram for the miniature implanted neurostimulatorwith RF telemetry (45). Rather than using inductive telemetry, the ASICcan provide RF telemetry. The RF output of the ASIC can be coupled viaRF coupling capacitor (43) to the TIP electrode connection (41). RFenergy can then be coupled to the flexible insulated lead wire (notshown) which can acts as an antenna. Alternatively, the electronicshousing case can be made from ceramic (to allow the passage of RF), anda RF magnetic loop antenna could be realized within the electronicscompartment. Other components such as a quartz crystal and additionalpassive components to generate and store the stimulator tank voltage maybe provided as well but are not shown for clarity. Also not shown arethe passive components, filter and crystal which may be provided toimplement a RF transceiver. Also not shown are addition sensors such asa GMR sensor which may be provided to disable therapy and preventinteractions with MRI. Nor is there shown an accelerometer to detect legmovements when required to delay therapy. Which such aforementionedcomponents are not shown, one or more of the components may be providedin the implanted miniature neurostimulators described above and herein.

An exemplary block diagram of the ASIC (50) is shown in FIG. 9 . Powerfrom a primary CFx cell can be supplied to the ASIC (50) through acharge and voltage monitor circuit (51). This circuit (51) can beresponsible for monitoring the cell voltage and the total charge thathas been withdrawn from the cell.

The output of the charge and voltage monitor circuit may feed theregulator (52) and charge pump (53). The regulator (52) may regulate thecell voltage, typically 3 V from a CFx cell to a lower voltage such as1.2 V, to power the remaining blocks of the system. The regulator (52)typically performs this down-conversion using a capacitive divider (notshown for clarity) to keep power supply efficiency high.

The processor (54) may contains a microprocessor, typically an 8-bit or16-bit core and may contain memory such as EEPROM, ROM, and static CMOSRAM provide storage for programs, programmable parameters, anddiagnostic information. The processor may interface with the voltage andcharge monitor circuit to provide a recommended replacement indicatorfor the physician. The processor may also control the charge pumpcircuit (53) and stimulation output circuit (55) and may communicatewith the implant telemetry circuit (58). The processor may alsointerface to a 32K oscillator (56). This oscillator typically runs at32768 Hz and may provide a clock reference for system functions. Theoscillator may use an external quartz crystal (59) to provide accuratetiming. The 32K oscillator may run continuously. A fast oscillator (57)may provide a clock to run the processor. This clock is usually 1 MHz orfaster and may only be enabled when the processor is active.Bidirectional telemetry may be performed by an implant telemetry circuit(58). The implant telemetry circuit can typically interface with aninductor in the embodiments with inductive telemetry. In the embodimentswith RF telemetry, a second ASIC reserved specifically for this functionis typically required although a single ASIC design could be realized.With RF telemetry, a handful of passive components, a SAW filter, and anadditional quartz crystal are typically required but are not shown forclarity.

The stimulation voltage required for the miniature implantedneurostimulator may be generated by the charge pump block (53). Thecharge pump may take the cell voltage and may generate a regulatedvoltage for stimulation. This regulated voltage may be higher or lowerthan the cell voltage. Typically, this regulation may be performed usinga capacitive charge pump configuration known to those skilled in theart. Two charge pump capacitors are shown (60, 61) although more may berequired. The output of the charge pump circuit may connect to thestimulator output circuit (55).

The stimulator output may generate either a constant voltage or constantcurrent waveform for stimulation. The use of an external DC-blockingcapacitor may ensure that the waveform is charge-balanced.

Other functions in the block diagram such as band-gap voltage source,current bias generators, and interfaces to other sensors such as a GMRsensor or accelerometer are not shown for clarity. The miniatureimplanted neurostimulator may be made possible because of the relativelylow duty-cycle required for a therapeutic benefit. PTNS stimulationtypically occurs for 30 minutes every week. This can translate to aduty-cycle of 0.5/168 or approximately 0.3%. Assuming a backgroundcurrent drain of 1 μA, a load resistance of 500Ω, a stimulation currentof 10 mA, stimulation frequency of 20 Hz, stimulation pulse width of 200μs and a cell capacity containing 230 mAH, for example, the miniatureimplanted neurostimulator will last more than 20 years.

Because of the low duty-cycle requirement, the longevity of the systemmay be very sensitive to the background current drain. The lowbackground current drain may be due to the fact that only the Q, Vmonitor circuit (51), 32 K oscillator (56) circuit, and implanttelemetry circuit (58) are typically always active. All other blocks canbe disabled, consuming only static leakage current. It is notunreasonable to assume the following quiescent current drain for eachblock:

-   -   ≤100 nA for the Q, V monitor circuit (51),    -   ≤250 nA for the 32 K oscillator circuit (56),    -   ≤500 nA for the implant telemetry circuit (58),    -   ≤100 nA for static CMOS leakage at 37° C.

The total estimated background current may be 950 nA or less than 1 μA.It is not unreasonable to push these numbers down even further. Withaggressive duty-cycling techniques the current drain for the Q, Vmonitor circuit and implant telemetry circuit could be reduced muchfurther.

Another consideration for the miniature implanted neurostimulator may bethe peak current taken from the cell. For a CFx cell of this size, thecell internal resistance is typically on the order of several hundredohms. Therefore, the peak current from each of the functional blocksdescribed in FIG. 9 should not cause the terminal voltage of the cell todrop below the useful minimum voltage. For example, if the lowestterminal voltage that could power the system is 2.0 V, then for atypical cell voltage of 3 V at beginning of service and a recommendedreplacement voltage of 2.5 V, the total peak current from the cell shallnot exceed (2.5 V-2.0 V)/300 ohm=1.67 mA for all features in the deviceto work correctly at the recommended replacement time. The functionalblocks which may require significant peak current from the cell are thefollowing:

-   -   Charge pump. Delivering 10 mA at 20 Hz from a compliance of 5 V        may require a capacitive multiplier circuit that doubles the        cell voltage. During stimulation, the peak current from the cell        may then be 10 mA*20 Hz*200 μs*2=80 μA, assuming 100%        efficiency. Even at an efficiency of 20%, the peak current may        only be 100 μA.    -   Implant telemetry. In the case of inductive telemetry, the peak        current may be estimated to not exceed 200 μA during transmit.        The receive current is typically not expected to exceed 50 μA.        However, the use of MICS RF telemetry typically requires        approximately 5 mA during either receive or transmit, thus        exceeding the peak current requirements. To avoid this peak        current, the Bluetooth Low Energy (BLE) protocol combined with        an external decoupling capacitor across the cell terminal can be        sufficient to reduce the cell peak current to an acceptable        value. For example, a typical BLE peak current profile suitable        for use in a miniature implanted neurostimulator is:        -   Pre-processing: 8 mA, 2 ms        -   TX/RX: 15 mA, 1 ms        -   Post-processing: 8 mA, 2 ms        -   Sleep: 0.1 μA, 20 s    -   This profile would yield an average current of less than 1 μA        and, when combined with a decoupling capacitor across the cell        of 100 μF, would only result a voltage drop of [(8 mA*4 ms)+(15        mA*1 ms)]/100 μF=0.47 V, allowing RF communication at the        recommended replacement time and still have the cell terminal        voltage exceed the 2.0 V minimum.

Although the processor block consumes 50 to 100 μA peak when active,this peak current may be supplied from a regulated supply with its owndecoupling capacitor. The firmware design and capacitor size can beoptimized to ensure that voltage drop in the regulated supply is on theorder of tens of millivolts.

FIG. 16 shows a state diagram for a low duty-cycle stimulator (125).Upon initialization, the stimulator can enter the IDLE state (126).After one week (128), the IDLE state can transition to the ENABLE STIMstate (127). In this state, the miniature implanted neurostimulator candeliver pre-programmed neurostimulation therapy to the patient. After 30minutes expires (129), the stimulator can transition back to the IDLEstate (126).

FIG. 17 shows a state diagram for a low duty-cycle stimulator withdeferred therapy (130). In this embodiment, an accelerometer may beincluded in the miniature implanted neurostimulator to detect limbmovement. Upon initialization, the stimulator may enter the IDLE state(131). After one week (134), the IDLE state may transition of the ENABLESTIM state (132). In this state, the miniature implanted neurostimulatorcan deliver pre-programmed neurostimulation therapy to the patient. Ifat any time during the therapy a leg movement is detected (137), theENABLE STIM state can be exited to a 1 HR DELAY state. After 1 hourexpires (136), simulation can be resumed by returning to the ENABLE STIMstate (132). After 30 minutes of stimulation (135), the stimulator cantransition back to IDLE state (131).

In some embodiments, neurostimulation therapy could be delivered whenthe patient is sleeping. The miniature implanted neurostimulator couldcontain a real-time clock that is programmed by the physician to delivertherapy at a time likely to coincide with the patient's sleep habits.

Although a miniature implanted neurostimulators that uses primary cellis described, a secondary (rechargeable) cell may be used in someembodiments.

Because of the low duty-cycle requirement of the therapy (0.3%), othertechnologies that allow for an implanted electrode to delivery therapyfrom an external power source may be provided. Magnetic, ultrasonic andRF technologies potentially allow for an even smaller implanted deviceto be placed on or near the sacral nerve for the purposes of treatingurinary or bowel incontinence. The smaller implanted device may even bedelivered via a percutaneous needle delivery system. In these cases, anexternal device may be present and held in reasonable proximity to theimplanted device to allow the transfer of energy.

II. Programmer

An exemplary external programmer is shown in FIG. 10 . FIG. 10 shows acuff-like housing that can encircle the limb containing the miniatureimplanted neurostimulator. The limb wand (65) shown by FIG. 10 maycomprise a wand main housing (66) and a flexible strap (67). The housingand strap may implement a toroidal coil configuration that encircles thelimb, such that its magnetic field can align with the magnetic field ofthe implanted neurostimulator's telemetry inductor, which can also alignwith the long axis of the neurostimulator. The strap (67) may containferrite material to form a highly permeable magnetic path completelyencircling a limb. Aligning the magnetic fields of both the implantedneurostimulator and limb wand (65) can provide optimal coupling and canresult in more reliable communication without the troublesome need toposition the wand as in inductive telemetry systems.

As shown in FIG. 11 , an exemplary limb wand (70) may completelyencircle the patient's leg. The programmer's telemetry coil (not shown),contained inside the housing (71), can completely encircle the leg andcan avoid the flexible strap. The limb wand (70) must be placed over thepatient's foot and ankle before it is positioned along the leg and inproximity to the miniature implanted neurostimulator.

The limb wands (65, 70) shown in FIG. 10 or 11 may contain the inductivecommunications circuitry needed to communicate with the miniatureimplanted neurostimulator and may also contain additional RF circuitryto relay the bi-directional communication with the implant to a smartphone, desktop, laptop or tablet computer via Bluetooth low energy orequivalent. The limb wand can be completely self-contained and may actas a relay such that an ordinary smart phone communicates with theinductive-telemetry-based miniature implanted neurostimulator via thelimb wand.

The block diagram (110) for such relay embodiments is shown in FIG. 15 .The limb wand may contain a battery (118) connected via an on/off switch(119) to a power supply (111). A processor (113) may contain an 8, 16,or 32-bit microprocessor and memory such as EEPROM, ROM, and static CMOSRAM to provide storage for programs. An oscillator (116) is may beconnected to the processor (113) to provide a system clock.

The processor (113) may communicate with an implant telemetry block(115) containing circuitry to communicate with the miniature implantedneurostimulator. The output of the implant telemetry block may connectto an inductor (121). The processor (113) may also communicate with anRF telemetry block (114) to communicate with a smart phone (114). Theoutput of the RF telemetry block may connect to an RF antenna (120). Theantenna may be an electric field or magnetic field antenna and the RFtelemetry system may contain more than one antenna for the purpose ofimplementing diversity.

The processor (113) may also communicate with a keyboard and displayblock (117) to provide I/O. An example of one display LED (122) and onekey input (123) is shown in FIG. 15 although more may be provided.Although an LED implementation is shown in FIG. 13 , LCD or othertechnology could also be used.

The processor (113) in the limb wand may also connect to monitor thebattery voltage (112) and can provide an indicator to the physician thatthe internal battery needs to be replaced in the case of primary cells,or to indicate that the internal battery needs recharging in the case ofsecondary cells.

An audible feedback transducer may be anticipated for the programmer butthe implementation is not shown.

FIG. 21 shows an exemplary smartphone programmer system (170) workingwith the patient's leg (171). The system (170) may comprise theminiature implanted neurostimulator (172), the limb wand (174), and thesmartphone programmer (173). The smartphone (173) may be used as theprogrammer, and communications with an inductive based miniatureimplanted neurostimulator can occur through the limb wand (174) that canact as a relay to allow the RF based smartphone (173) to communicatewith the inductive based miniature implanted neurostimulator.

FIG. 12 shows another exemplary external programmer (75). Here, the keyinput and display output (77) may be integrated into the torsoprogrammer (75). The programmer main housing (76) is shown along withthe flexible strap (78). Just as in the limb wand, the torso programmer(75) can allow the alignment of the programmer and miniature implantedneurostimulator for more reliable communication when an inductivetelemetry scheme is used.

FIG. 13 shows another exemplary external programmer (80). Here, theprogrammer (80) may contain electronics to receive input and displayoutput (84) such that the user can program and interrogate the miniatureimplanted neurostimulator. Additionally, the programmer may incorporatea neurostimulator generator for delivering PTNS therapy during anevaluation phase that may be required before a patient is implanted witha device. The programmer (80) may communicate with the implant via RFtelemetry such as that shown and described above with reference to FIG.3 or 4 , or the programmer may connect to a limb wand such as that shownand described above with reference to FIG. 10 via RF or a cable (81)(connection not shown in FIG. 10 ).

This programmer/neurostimulator (80) can provide a TIP (82) and RING(83) connection that may be connected to a transcutaneous needle andadhesive patch electrode respectively for the purpose of demonstratingthe efficacy of the neurostimulation therapy.

The block diagram for a programmer with integrated PTNS generator (85)is shown in FIG. 14 . The programmer (85) may contains a battery (95)connected via an on/off switch (96) to a power supply (86) to provide aregulated voltage. A processor (90) may contain an 8, 16 or 32-bitmicroprocessor and memory such as EEPROM, ROM and static CMOS RAM toprovide storage for programs. An oscillator (91) can be used to providea system clock. A real-time clock (92) may also be provided to allowreal-time events to be programmed in the miniature implantedneurostimulator.

The processor (90) may communicate with an implant telemetry block (93)containing circuitry to communicate with the miniature implantedneurostimulator. This implant telemetry block may connect to an inductorfor communication with an inductive based miniature implantedneurostimulator. In the case of an RF based miniature implantedneurostimulator, the implant telemetry circuitry may contain an RFtransceiver and may connect to one or more RF antennas. Alternatively,the implant telemetry circuitry may provide for a hardwire connection tothe limb wand.

The processor (90) may also control the charge pump (87) and stimulatoroutput circuitry (89). The charge pump may take the regulated voltagefrom the power supply (86) and may generate a regulated voltage used forstimulation. Typically, this regulation may be performed using acapacitive charge pump configuration known to those skilled in the art.Two charge pump capacitors are shown (97, 98), although more may berequired. The output of the charge pump circuit may connect to thestimulator output circuit (89).

The processor (90) may also control the stimulation output circuitry(89). The stimulator output may generate either a constant voltage orconstant current waveform for stimulation. The use of a DC-blockingcapacitor (99) can ensure that the waveform is charge-balanced.

The processor may monitor the battery voltage (88) to provide anindicator to the physician that the internal battery needs to bereplaced in the case of primary cells or indicate that the internalbattery needs recharging in the case of secondary cells. The processor(90) may also communicate with the keyboard and display circuitry (94)to provide I/O. An example of one display LED (103) and one key input(104) is shown in FIG. 14 , although more may be provided. Although anLED implementation is shown in FIG. 14 , LCD or other technology couldalso be used.

III. Key Fob

An RF-based miniature implanted neurostimulator can also be activated bya patient operated key fob (140) as shown in FIG. 18 . The key fob (140)may comprise a housing (141), a key (144) that the patient presses toactivate the key fob action, an LED to indicate that the key fob isactive (142), and an LED to indicate when the key fob battery must bereplaced (143). The LED indicating that the key fob is active (142) maybe enabled when the key (144) is pressed, or may be enabled only whenthe key (144) is pressed and the key fob has confirmed that theminiature implanted neurostimulator has received the key fob command.The key fob may choose to distinguish between a single click, delayedhold, and a double click to send unique commands, or additional keys maybe included on the key fob for unique commands.

Activation of the key fob by the patient may result in a pre-programmedcommand to be executed by the miniature implanted neurostimulation.Commands may be selected and modified by the physician using theprogrammer. More than one command may be available to be executed by theminiature implanted neurostimulator.

An exemplary block diagram for the patient key fob (140) is shown inFIG. 19 . The key fob (140) may contain a battery (157) connected via anon/off switch (158) to a power supply (151) to provide a regulatedvoltage. A processor (153) may contain an 8, 16, or 32-bitmicroprocessor and memory such as EEPROM, ROM and static CMOS RAM toprovide storage for programs. An oscillator (155) may be used to providea system clock.

The processor (153) may communicate with an RF telemetry circuit (154)containing circuitry to communicate with an RF based miniature implantedneurostimulator. The RF telemetry block (154) may connect to an RFantenna (159).

The processor (153) may monitor the battery voltage (152) to provide anindicator to the user than the internal battery needs to be replaced inthe case or primary cells or indicate that the internal battery needsrecharging in the case of secondary cells. The processor (153) can alsocommunicate with a display driver (156) to illuminate one or more LEDsto indicate low-battery or that the transmitter is active. Only one LED(160) is shown in FIG. 19 ; however, more than one may be implemented.

An audible feedback transducer may be provided for the key fob, but theimplementation is not shown. In other embodiments, the dedicated key fobis replaced by a smartphone. In this case, the RF standard used by thesmartphone and the miniature implanted neurostimulator may be compatiblesuch as with BLE.

The smart phone/key fob system is shown in FIG. 20 . The human leg (166)and miniature implanted neurostimulator (167) and the patient activatedkey fob or smart phone (168) are illustrated. Either the key fob orsmartphone can communicate directly with the miniature implantedneurostimulator via RF.

IV. Hybrid Telemetry

As discussed above and herein, both RF and inductive telemetry schemescan be provided for the miniature implanted neurostimulator. In someembodiments, a hybrid scheme can be provided. The hybrid scheme canprovide for programmer-to-implant (P-to-I) communication to occur viamagnetic fields while implant-to-programmer (I-to-P) communicationoccurs via conductive telemetry. An advantage of such a system is thatbidirectional telemetry can be performed using a minimum number ofcomponents in the implant. For example, the I-to-P communicationschannel may start with a transmitter in the implant that reuses the samehardware and electrodes as used for neurostimulation and the P-to-Icommunications channel implant receiver can use a GMR sensor thatoccupies an area of only 1.1 mm by 1.1 mm. This configuration canprovide a simple and compact embodiment for bidirectional telemetry inan implanted neurostimulator.

An exemplary block diagram for the miniature implanted neurostimulatorthat supports this hybrid telemetry scheme is shown in FIG. 25 . Thecell (211) can power a microprocessor (212). Internal to themicroprocessor is typically a high frequency oscillator, typically 0.5to 8 MHz, to clock the internal core; however, an external 32K (32768Hz) crystal (226) is shown, which may provide a real-time clock todetermine stimulation pulse width and periods accurately. A voltageconverter/charger (214) is shown, which may convert the cell voltage toa higher voltage for stimulation. The charger (214) is typically a boostregulator that uses an inductor (216) to store energy when the SWterminal of (214) is connected to ground. The voltage can be boostedwhen the SW terminal is released from ground and the stored energy isreleased from the inductor and passes through the flyback diode (217),transferring the energy to the stimulation tank capacitor (218). Themicroprocessor (212) can provide a digital-to-analog converter (DAC)connected to the signal, TARGET. The resistor network (223, 224 and 225)may form an attenuator network providing a feedback signal (FB) to thecharger. The feedback signal may typically be compared to an internalreference voltage to regulate the voltage on the stimulation tankcapacitor (218). By varying the DAC voltage on TARGET, the stimulationvoltage can typically be set anywhere from 10 V to the cell voltageminus a diode drop. The microprocessor (212) can disable the voltageconverter/charger to conserve energy by de-asserting the EN signal. Theminiature implanted neurostimulator may provide stimulation by assertingthe STIM signal from the microprocessor and closing the stimulationpulse MOSFET switch (222). When the switch is closed, a monophasictruncated exponential pulse can be applied between the TIP (229) andRING (228) terminals. The stimulation pulse current can flow through acharge balancing capacitor (221) that accumulates charge during thestimulation pulse. Following stimulation, the charge stored on thecharge balancing capacitor can be discharged back through the RING andTIP via resistor (219). Diode (220) can provide protection againstelectrosurgery and other external influences that could affect theintegrity of the system. A giant magnetoresistance sensor (GMR) mayconnect to the microprocessor providing a signal, MAG_DET_B, when anexternal magnetic field is detected. The sensor can be enabled byasserting the GMR_EN signal. Pull-up resistor (275) may keep theopen-collector output of the sensor de-asserted.

I-to-P communication can occur via conducted communications using theidentical circuitry to create stimulation pulses between the RING andTIP electrodes. Information can be sent by the implantable stimulator byapplying short (typically 10 to 15 μs) pulses between the TIP and RINGterminals such that the stimulation pulses are sub-threshold and have notherapeutic value. The electric field generated between the TIP and RINGterminals can then be detected on the skin surface by the programmer anddecoded for use in an I-to-P communication channel. In this example, theimplant has two electrodes, but alternative embodiments with more thantwo electrodes could also be used.

FIG. 27 illustrates I-to-P communication. The miniature implantedneurostimulator (241) is shown with TIP and RING electrode connections.The skin barrier (242) is shown to highlight that the programmer skinelectrodes can pick-up a far-field signal generated by the TIP and RINGelectrodes, and that I-to-P communications can occur wirelessly fromimplant to programmer, albeit with the use of electrodes placed on thesurface of the skin. FIG. 27 shows an amplifier/filter (244) connectedto the programmer skin electrodes. In this example, the programmer usestwo skin electrodes, but alternative embodiments with more than two skinelectrodes could also be used. For example, the programmer couldautomatically select the electrode configuration that provides theoptimal signal strength or signal to noise ratio.

The output of the amplifier/filter may connect to a detector (245),whose output is a decoded signal, RX_DATA. The detector could be asimple comparator whose output is asserted when the signal exceeds apredetermined threshold. FIG. 27 shows a simplified example of the basicsignal processing that can be used to decode the I-to-P signal. Thisprocessing could be performed using analog circuitry, digital circuitry,software, or a combination thereof. The amplifier/filter (244) can alsocontain input protection circuitry (not shown).

Stimulation at approximately 2.5 V by the implant will result in amillivolt level signal appearing on the skin surface. Therefore, a gainof approximately 3000 may be required for the amplification shown byFIG. 27 . Although more sophisticated filter approaches can be appliedeither in the analog or digital domains, a simple band-pass filter, witha low-pass corner set to acquire 90% of the pulse amplitude within thefirst 10% of the pulse duration, assuming a 10 μs pulse, can give alow-pass corner of 300 kHz. The high-pass corner may be set with thelonger 15 μs pulse such that the pulse sags only ⅓rd, resulting in ahigh-pass corner of 10 kHz.

P-to-I communication can occur via magnetic fields generated by theprogrammer. Modulation of magnetic fields by the programmer, forexample, by the use of an electromagnet, may be detected in theimplantable stimulator by the GMR sensor, creating a P-to-Icommunications channel. FIG. 26 illustrates P-to-I communication. Theprogrammer hardware may generate a data signal, TX_DATA, which mayenable a programmer transmit switch (231) and may energize anelectromagnetic (233). Flyback diode (232) may act as a snubber,protecting the programmer switch (231). The skin barrier (242) is shownin FIG. 26 to highlight that the external electromagnet and GMR sensormay be separated by a short distance, typically 2 to 10 cm, and thatP-to-I communication may occur wirelessly from programmer to implant.FIG. 26 also identifies the GMR sensor located in the miniatureimplantable neurostimulator. The output of the GMR sensor, MAG_DET_B,can convey the information sent by the signal TX_DATA.

In an example, the electromagnet may comprise a soft-iron core solenoid,where the cross-section of the core is 0.8 cm² in diameter, 14 cm inlength with an air gap of 4 cm. With a relative permeability of ironequal to 200, the reluctance of the core may be approximately 6.1 (1/μH)and the reluctance of the air gap may be approximately 354 (1/μH). For acoil with 300 turns on the iron core with a peak current of 3 A, theresulting magnetomotive force, F, may be equal to 900 Wb/H. The totalflux, φ, can be given by F/R, where R is the reluctance of the iron coreand the air gap combined. The total flux may be 2.5 μWb. The fluxdensity in air may be given by the relationship, B=φ/RAIR, which maygive a flux density in air of approximately 28 mT. The GMR sensor usedmay be, for example, a BD927-14E, manufactured by NVE Corporation, EdenPrairie Minn. This sensor has a typical operating point of 15 Oersteds,which corresponds to 1.5 mT. The flux density across the air gap of theelectromagnet may be sufficient to trigger the GMR, even at the locationof the implant, which is off-axis with respect to the magnet's air gap.

The sensor may have a typical quiescent current drain at 2.4 V equal to75 μA. To conserve energy, the microprocessor (212) in the FIG. 25 blockdiagram may enable the sensor only at infrequent intervals. However,since the GMR sensor may be enabled for a relatively short period, theprogrammer may not know when the GMR sensor is active. To solve this,the implant may provide a synchronization pulse to the programmer,letting the programmer know when to enable the electromagnet and sendinformation back to the programmer. This process is first demonstratedin FIG. 28 . Here, the miniature implantable neurostimulator can send asubthreshold pulse between the RING and TIP electrodes with a pulsewidth of 10 μs. This short pulse may be sent every 10 seconds by theimplant during periods that are otherwise inactive. The amplitude of thepulse is typically the cell voltage minus one diode drop. The implantcan enable the GMR sensor following each short pulse, looking forconfirmation that a programmer is present.

If no programmer is present, the implant may simply continue sendingshort pulses every 10 seconds between the RING and TIP. The energyconsumed during this short pulse and the energy consumed by enabling theGMR sensor relatively infrequently may be negligible.

However, when a programmer is present, e.g., when skin electrodes areconnected to the limb near the implant site and the programmer wand ispositioned close to the implant, the programmer may detect the shortpulses. Therefore, the programmer can enable the programmer'selectromagnet when the implant's GMR sensor is active. In this way, alink can be established between the programmer and implant. When theimplant detects a magnetic pulse using the GMR sensor, the implant cansend short pulses between the RING and TIP every 50 ms. In this way,data throughput in both directions can be increased. FIG. 29 shows theminiature implanted neurostimulator sending short pulses (10 μs) betweenRING and TIP but at a rate of 20 Hz. The implant may also enable the GMRsensor following each short pulse to look for data being sent from theprogrammer via an electromagnet.

Communication can also occur while the miniature implantedneurostimulator is delivering therapy. An example of this is shown inFIG. 30 . The RING-TIP signal may show short 10 μs pulses occurringevery 50 ms. After each short pulse, a longer, therapeutic stimulationpulse with a duration of 200 μs may occur. The programmer candistinguish the short, subthreshold pulses from the longer therapeuticpulses.

An example of I-to-P data communication is shown in FIG. 31 . FIG. 31shows a data “1” identified as a short 10 μs pulse, while a data “0” isidentified as a longer, 15 μs, but still subthreshold, pulse absent bythe implant. The programmer may receive this signal via two or more skinelectrodes and amplifies and filters this signal. The received signalbefore detection is shown as the signal RX. The detector and associatedprocessing circuitry and/or software can distinguish short (10 μs)pulses from long (15 μs) pulses and outputs a “1” following each shortpulse and a “0” following a long pulse. The RX_DATA signal in FIG. 31illustrates this.

An example of I-to-P data communication during neurostimulation therapyis shown in FIG. 32 . FIG. 32 shows a data “1” identified as a short 10μs pulse, followed by a 200 μs therapeutic pulse. After the first 50 ms,it shows a data “0” identified as a longer 15 μs pulse again followed bya 200 μs pulse. After amplification and filtering, the programmer mayprovide the RX signal as a faithful reproduction of theimplant-generated waveform. The detector and associated processingcircuitry and/or software may distinguish short (10 μs) from long (15μs) pulses and may be refractory to even longer (200 μs) therapeuticpulses. The RX_DATA signal in FIG. 32 illustrates this concept.

An example of P-to-I data communication is shown in FIG. 33 . FIG. 33shows three short (10 μs) synchronization pulses send by the implant.When the implant is expecting to receive data, the GMR sensor may beactivated following each synchronization pulse. The programmer can thensend data at the correct time for detection by the implant. An exampleof this is shown by the signal TX_DATA in FIG. 33 . The programmer maysend a data “0” following the first pulse (a) by asserting TX_DATA, maysend a data “1” by not asserting TX_DATA following the second pulse (b),and may send another data “0” following the third pulse (c) by assertingTX_DATA. The received electromagnetic signal, MAG_DET is shown. Themicroprocessor may acknowledge a data “0” following the assertion of theMAG_DET_B signal after the first pulse. Since no assertion of MAG_DET_Boccurred following the second pulse, the microprocessor may interpretthis as a data “1” and so on.

An example of P-to-I data communication during neurostimulation therapyis shown in FIG. 34 . FIG. 34 shows a short (10 μs) synchronizationpulse followed by a 200 μs therapeutic pulse. After 50 ms, it showsanother short synchronization pulse followed by another therapeuticpulse. After the first synchronization pulse, the programmer may send adata “0” by asserting TX_DATA. After the second synchronization pulse,the programmer may send a data “1” by not asserting TX_DATA. Thereceived electromagnetic signal, MAG_DET_B is shown. Since theprogrammer's detector and associated processing circuitry and/orsoftware may distinguish short synchronization pulses from longtherapeutic pulses, the programmer may assert TX_DATA following eachsynchronization pulse when a data “0” is required and may not assertTX_DATA following synchronization pulses when a data “1” is required.

In this example, only one symbol is sent per bit. Therefore, the symbolrate and data rate may be equal and set to 20 Hz. This data rate waschosen to coincide with the stimulation frequency, greatly simplifyingthe transmission and reception of data. However, the number of symbolsper bit could be increased with different modulation schemes and therate could be increased beyond the stimulation frequency with addedcomplexity.

An exemplary method to decode the data streams received by the implantand by the programmer may be to format the data in non-return-to-zero(NRZ) serial format and use a serial universal asynchronousreceiver/transmitter (UART). An example of this is shown in FIG. 35 .When used with a serial UART, NRZ data format follows the convention ofsending a start bit, followed typically by 8 data bits, starting fromLSB (D0) to MSB (D7), followed by a at least one stop bit. Often theformat may provide an additional parity bit. This example may use onestart bit, one stop bit and no parity bit, as seen by trace a) in FIG.33 . In the first example, I-to-P data communication is shown in tracesb and c. Trace b) shows short (10 μs) pulses to indicate a data “1” andlong (15 μs) pulses to indicate a data “0”. Typically, a data “1” wouldbe sent prior to the transmission of the start bit. The first occurrenceof a data “0” (long, 15 μs pulse) may indicate the start bit. Theprogrammer may receive and interpret the implant signal by generatingRX_DATA as seen in trace c). The data byte received by the programmermay be decoded as 0xA5. In the second example, P-to-I data communicationis shown in traces d), e), and f). Trace d) shows short (10 μs)synchronization pulses send by the implant. Trace e) shows TX_DATA,where data “0s” are occasionally sent following a synchronization pulse.In this example, a data “0” is sent following the synchronization pulsesfor the start bit, bits D1, D3, D4, and D6. The received electromagneticsignal may be captured by the GMR detector and shown in trace f, signalMAG_DET_B. The data byte received by the implant may be decoded as 0xA5.

This example describes half-duplex communication, where I-to-P or P-to-Icommunication may be mutually exclusive. Because the communicationmethods used in the physical layer may be independent, electromagneticin the case of P-to-I and conducted in the case of I-to-P, full-duplexcommunication can be easily achieved. The programmer may be able tosynchronize not only to short (10 μs) pulses identified as a data “1”for I to P communication but also to synchronize to long (15 μs) pulsedidentified as a data “0” for I to P communication.

This example describes only the physical layer and a rudimentary datalink layer typical of an ISO network protocol. The remaining layers arecontemplated but not described here. Typically, an end-to-end protocolis implemented, complete with checks to ensure data integrity andenhancements to provide communications in the presence of noise.

Embodiments provide for a programmer implemented in various physicalembodiments. In some embodiments, all the elements required forprogrammer operation are contained in a single housing. In someembodiments, some of the elements are contained in a first housing andother elements are contained in a second housing intended for placementnear the implant, called a “wand”. In some embodiments, the two housingsmay be connected by a cable or by wireless means. In some embodiments, athird housing contains a power supply. For convenience the followingdescription refers to the ensemble of elements as a “programmer/wand”.

The programmer/wand block diagram is shown in FIG. 36 . In this example,the programmer/wand comprises a battery (251) connected via an on/offswitch (252) to a power supply (253). A processor (255) comprises an8-bit, 16 or 32-bit microprocessor and memory such as EEPROM, ROM andstatic CMOS RAM to provide storage for programs. An oscillator (256) isshown connected to the processor to provide a system clock.

The processor may send information to the implant by asserting TX_DATAand driving the electromagnetic assembly composed of switch (262),electromagnet (260), and snubber diode (261). The microprocessor mayreceive information from the implant by detecting conducted telemetrysignals on the skin electrodes (265) connected to the amplifier/filter(259), detecting these signals (258) and decoding the RX_DATA signal.

The processor may also communicate with a keyboard and display block(257) to provide user input/output (I/O). An example of one output LED(263) and one input key (264) is shown although more may be provided.Although an LED implementation is shown, LCD or other technology couldalso be used.

The programmer/wand also may not contain a keyboard and display unit butrather provide a USB connection or Bluetooth connection to a tabletwhere the keyboard and display unit may reside.

The processor in the limb wand may also connect to monitor the batteryvoltage (254) and may provide an indicator to the physician that theinternal battery needs to be replaced in the case of primary cells, orto indicate that the internal battery needs recharging in the case ofsecondary cells.

An audible feedback transducer may be provided for the programmer.

While preferred embodiments of the present disclosure have been shownand described herein, it will be obvious to those skilled in the artthat such embodiments are provided by way of example only. Numerousvariations, changes, and substitutions will now occur to those skilledin the art without departing from the invention. It should be understoodthat various alternatives to the embodiments of the present disclosuredescribed herein may be employed in practicing the inventions of thepresent disclosure. It is intended that the following claims define thescope of the invention and that methods and structures within the scopeof these claims and their equivalents be covered thereby.

What is claimed is:
 1. A method of treating an overactive bladdercondition, the method comprising: providing a stimulation devicecomprising a generator enclosing a primary cell that is coupled tocircuitry, and a lead coupling an electrode assembly to the generator,where the circuitry is operable to generate a stimulation signal with aduty cycle of between 0.1% and 2.5% and a total average current drainfrom the primary cell of between 0.1 μA and 5 μA, with the total averagecurrent drain comprising a background current plus a stimulation currentweighted by the duty cycle; forming an incision in skin of a patientdiagnosed with the overactive bladder condition; implanting thestimulation device in the patient by inserting the stimulation deviceinto the incision in the skin of the patient; and closing the incision.2. The method of claim 1, wherein the electrode assembly furthercomprises a proximal electrode and a distal electrode, the methodfurther comprising: forming a first tunnel from the incision into a legof the patient and a second tunnel distal relative to the first tunnel;placing the generator in the first tunnel; and placing the electrodeassembly in the second tunnel with the distal electrode located at oradjacent to a sciatic nerve or at or adjacent to a branch of the sciaticnerve.
 3. The method of claim 1, wherein the electrode assembly furthercomprises a proximal electrode and a distal electrode, and whereinforming the incision in the skin of the patient comprises forming aprimary incision in a leg of the patient and forming a secondaryincision in the leg of the patient, the method further comprising:forming a tunnel extending from the primary incision to the secondaryincision; advancing the generator into the tunnel; advancing theelectrode assembly into the tunnel and positioning the distal electrodeat or adjacent to a tibial nerve or a branch of a sciatic nerve; andcoupling the generator with the electrode assembly.
 4. The method ofclaim 1, further comprising: forming a first tunnel from the incisioninto a leg of the patient and a second tunnel distal relative to thefirst tunnel; placing the generator in the first tunnel; placing theelectrode assembly in the second tunnel and locating an electrode of theelectrode assembly at or adjacent a tibial nerve; and fixating theelectrode assembly to the second tunnel by anchoring a fixation elementof the electrode assembly within the second tunnel.
 5. The method ofclaim 1, further comprising: forming a first tunnel from the incisioninto a leg of the patient and a second tunnel distal relative to thefirst tunnel; placing the generator in the first tunnel; placing theelectrode assembly in the second tunnel and locating an electrode of theelectrode assembly at or adjacent a tibial nerve; and fixating theelectrode at or adjacent the tibial nerve by tying a suture to theelectrode assembly and anchoring the suture to tissue.
 6. The method ofclaim 1, further comprising: forming a first tunnel from the incisioninto a leg of the patient and a second tunnel distal relative to thefirst tunnel; placing the generator in the first tunnel; placing theelectrode assembly in the second tunnel; and fixating the generator tothe first tunnel by anchoring a fixation element of the generator to thefirst tunnel.
 7. The method of claim 1, further comprising: providing anexternal programmer; and wirelessly communicating between the externalprogrammer and the stimulation device one or more of a voltage of theprimary cell, a therapy status, a command from the external programmerto the stimulation device, a therapy schedule, and a synchronizationpulse between the external programmer and the stimulation device.
 8. Themethod of claim 1, further comprising: implanting the generator in a legof the patient and implanting the electrode assembly at or near a tibialnerve in the leg of the patient.
 9. The method of claim 1, furthercomprising: implanting the generator in a leg of the patient andimplanting the electrode assembly at or near a tibial nerve in the legof the patient; and using an external programmer to wirelessly initiatethe stimulation signal to begin tibial nerve stimulation therapy fortreating the overactive bladder condition.
 10. The method of claim 1,further comprising: implanting the generator in a leg of the patient andimplanting the electrode assembly at or near a tibial nerve in the legof the patient; and instructing the circuitry to the generate thestimulation signal causing the electrode assembly to stimulate thetibial nerve for about 30 minutes each week in treating the overactivebladder condition.
 11. The method of claim 1, further comprising:implanting the generator in a leg of the patient and implanting theelectrode assembly at or near a tibial nerve in the leg of the patient;and instructing the circuitry to the generate an initial frequency ofthe stimulation signal causing the electrode assembly to stimulate thetibial nerve more frequently than for about 30 minutes each week at astart of therapy, and then tapering to a second frequency of thestimulation signal causing the electrode assembly to stimulate thetibial nerve at about 30 minutes each week, thus treating the overactivebladder condition with a frequent stimulation after implantationfollowed by a less frequent stimulation at the second frequency.
 12. Amethod of treating an overactive bladder condition, the methodcomprising: providing a stimulation device comprising a generatorenclosing a primary cell that is coupled to circuitry, and a leadcoupling an electrode assembly to the generator, where the circuitry isoperable to generate a stimulation signal with a duty cycle of between0.1% and 2.5% and a total average current drain from the primary cell ofbetween 0.1 μA and 5 μA, with the total average current drain comprisinga background current plus a stimulation current weighted by the dutycycle; forming an incision in skin of a patient diagnosed with theoveractive bladder condition; forming a tunnel under the skin from theincision into a leg of the patient; placing the generator in the tunnel;placing a portion of the lead and the electrode assembly in the tunneland locating the electrode assembly at or adjacent to a posterior tibialnerve in the leg of the patient; closing the incision; and operating thecircuitry to generate the stimulation signal and causing the electrodeassembly to stimulate the posterior tibial nerve for about 30 minuteseach week in treating the overactive bladder condition.
 13. The methodof claim 12, further comprising operating the circuitry and stimulatingthe posterior tibial nerve for about 30 minutes each week for at least 5years without removing the stimulation device from the patient.
 14. Themethod of claim 12, further comprising operating the circuitry andstimulating the posterior tibial nerve for about 30 minutes each weekwithout removing the stimulation device from the patient by configuringthe stimulation device to have a longevity exceeding 5 years.